Lipids in critical care medicine

https://doi.org/10.1016/j.plefa.2011.04.011Get rights and content

Abstract

While enteral nutrition is the basis for the critically ill, parenteral nutrition is often used when a sufficient enteral nutrition is not or not fully achievable. Lipids are a mainstay of caloric supply in both cases as they combine the provision of building blocks for the membranes and are precursors for function molecules including lipid mediators bearing the ability to influence immunity. Pro-inflammatory lipid mediators as prostaglandins and leukotrienes are generated from arachidonic acid (AA), a key member of the n-6 polyunsaturated fatty acids (PUFA). In contrast, lipid mediators derived from the n-3 fatty acids eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) may exhibit less inflammatory properties compared to their AA-derived counterparts. Furthermore, intercellular mediators as resolvins and protectins are generated from n-3 fatty acids. They induce the resolution of inflammation, hence the name resolution phase interaction product—resolvin. Modulating the amount of PUFA and the n-6/n-3 ratio were investigated as means to change the inflammatory response and improve the outcome of patients. Experimental data showed that n-3 fatty acids may improve acute lung injury and sepsis in animal models. Studies in patients undergoing major surgery with application of n-3 fatty acids demonstrated beneficial effects in terms of reduction of length of stay and infectious complications. Clinical data hints that this concept may also improve outcome in critically ill patients. Additionally, experimental and clinical data suggest that a reduction in n-6 PUFA may change the immune response. In conclusion, modulating the amount of PUFA, the n-6/n-3 ratio and the composition of lipid emulsions may prove to be a useful means to improve the outcome of critically ill patients.

Section snippets

Lipids in clinical nutrition

Nutrition of critical ill patients in intensive care units is a vital element and needs to be reflected. To fully support the caloric expenditure lipids and lipid emulsions play an essential role in the diet not only due to their high caloric content, but also because lipids are crucial for cell membrane composition. Furthermore, fatty acids display modulatory effects on the immune system. Current publications showed beneficial effects for critically ill patients when fish oil is added to their

Biochemical background of lipid mediators based on arachidonic acid (AA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)

Local-acting lipid mediators involved in the regulation of inflammation are derived from the semi-essential polyunsaturated fatty acids AA, EPA and DHA. Oxidation of these substrates by cyclooxygenase, lipoxygenase, and cytochrome P-450 produces prostaglandins, leukotrienes, lipoxins, resolvins and protectins (Fig. 1). These mediators act as intercellular signaling molecules which possess either pro- or anti-inflammatory effects [10], [11]. While most AA-derived mediators aggravate

Resolvins improve course of inflammation and facilitate reconstitution of homeostasis

Resolvins dampen course and enhance resolution of inflammation via several different mechanisms. They reduce neutrophil extravasation and invasion to inflammatory sites by attenuating expression of adhesion molecules and stimulation of endothelial nitric oxide synthase (NOS) [17]. At loci of inflammation the pro-inflammatory impact of neutrophils is alleviated due to a reduced activation of NF-κB. Hence, production of pro-inflammatory cytokines like TNF-α and interleukin 1. Furthermore they are

The benefits of supplemented n-3 lipids in surgical patients

Recent studies promoted the use of n-3 lipids in surgical patients [29], [30], [31]. Checking the safety profile of lipid emulsions containing n-3 fatty acids, 44 patients with abdominal surgery of a single center study received either a lipid emulsion rich in n-6 fatty acids (SO) or SO supplemented with n-3 lipids (FO) for five days after the surgery. Up to a dose of 0.2 g FO/g bodyweight/d no coagulation or platelet abnormalities were triggered [29]. Adding to the safety profile, changes in

Acute lung injury (ALI/ARDS) and n-3 fatty acids

Acute lung injury (ALI) or the more severe form acute respiratory distress syndrome (ARDS) is defined by clinical, radiological and physiological findings. There are bilateral infiltrates in the lung and a pulmonary capillary wedge pressure below 18 mmHg. The differentiation between ALI and ARDS is defined by the oxygenation index of the arterial oxygen partial pressure (PaO2) divided by the inspiratory oxygen concentration (FiO2). In ALI the PaO2/FiO2 displays values less than 300 mmHg, compared

Sepsis and the advantage of employing n-3 fatty acids

Sepsis is a serious and complex inflammatory process that is characterized by a systemic inflammatory response to the presence of an infection. In intensive care units, the disease counts as the leading cause of death. Mortality ranges between 30% and 60% with around 750,000 new diagnosed cases annually in the USA [54], [55], [56]. In the course of the disease, initially a massive hyper-inflammatory response (systemic inflammatory response syndrome—SIRS) triggered not only by the microbial

Conclusion

Expanding knowledge during the past years of the metabolic, biochemical and immunological capacities of lipids and lipid emulsions in patients has driven the development of new mixture lipid emulsions. Up to date various compositions are available. The variable components show different properties that are desirable in diet and treatment of critically ill. Olive Oil, MCT, and FO have the ability to counterbalance the harmful effects of n-6 fatty acids and SO in regard of immunological effects.

References (74)

  • J.C. Jaume

    Extremely low doses of heparin release lipase activity into the plasma and can thereby cause artifactual elevations in the serum-free thyroxine concentration as measured by equilibrium dialysis

    Thyroid

    (1996)
  • C. Weissman

    The metabolic response to stress: an overview and update

    Anesthesiology

    (1990)
  • J.A. Lovegrove

    Use of manufactured foods enriched with fish oils as a means of increasing long-chain n-3 polyunsaturated fatty acid intake

    Br. J. Nutr.

    (1997)
  • K. Mayer

    Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation

    Intensive Care Med.

    (2003)
  • M. Abbey

    Effect of fish oil on lipoproteins, lecithin:cholesterol acyltransferase, and lipid transfer protein activity in humans

    Arteriosclerosis

    (1990)
  • K. Qi

    Omega-3 triglycerides modify blood clearance and tissue targeting pathways of lipid emulsions

    Biochemistry

    (2002)
  • J.W. Sijben et al.

    Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease

    Proc. Nutr. Soc.

    (2007)
  • K. Mayer et al.

    Fish oil in critical illness

    Curr. Opin. Clin. Nutr. Metab. Care

    (2008)
  • P.C. Calder

    N-3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic

    Lipids

    (2003)
  • S.M. Prescott et al.

    Fish oil fix

    Nat. Med.

    (2005)
  • M. Spite

    Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

    Nature

    (2009)
  • H. Hasturk

    Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo

    J. Immunol.

    (2007)
  • R.J. Flower et al.

    Controlling inflammation: a fat chance?

    J. Exp. Med.

    (2005)
  • C.N. Serhan et al.

    Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators

    Nat. Rev. Immunol.

    (2008)
  • G.L. Bannenberg

    Molecular circuits of resolution: formation and actions of resolvins and protectins

    J. Immunol.

    (2005)
  • M. Arita

    Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1

    J. Exp. Med.

    (2005)
  • J.M. Schwab

    Resolvin E1 and protectin D1 activate inflammation-resolution programmes

    Nature

    (2007)
  • H. Seki

    The anti-inflammatory and proresolving mediator resolvin E1 protects mice from bacterial pneumonia and acute lung injury

    J. Immunol.

    (2009)
  • O. Haworth et al.

    Endogenous lipid mediators in the resolution of airway inflammation

    Eur. Respir. J.

    (2007)
  • B.D. Levy

    Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness

    J. Immunol.

    (2007)
  • K.M. Connor

    Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis

    Nat. Med.

    (2007)
  • H. Tian

    Resolvins E1 and D1 in choroid-retinal endothelial cells and leukocytes: biosynthesis and mechanisms of anti-inflammatory actions

    Invest. Ophthalmol. Vis. Sci.

    (2009)
  • A.R. Heller

    Impact of n-3 fatty acid supplemented parenteral nutrition on haemostasis patterns after major abdominal surgery

    Br. J. Nutr.

    (2002)
  • A.R. Heller

    Omega-3 fatty acids improve liver and pancreas function in postoperative cancer patients

    Int. J. Cancer

    (2004)
  • H. Antebi

    Liver function and plasma antioxidant status in intensive care unit patients requiring total parenteral nutrition: comparison of 2 fat emulsions

    J. Parenter. Enteral. Nutr.

    (2004)
  • H. Grimm

    Improved fatty acid and leukotriene pattern with a novel lipid emulsion in surgical patients

    Eur. J. Nutr.

    (2006)
  • M.M. Berger et al.

    Fish oil after abdominal aorta aneurysm surgery

    Eur. J. Clin. Nutr.

    (2008)
  • Cited by (45)

    • A four-oil intravenous lipid emulsion improves markers of liver function, triglyceride levels and shortens length of hospital stay in adults: a systematic review and meta-analysis

      2021, Nutrition Research
      Citation Excerpt :

      To our knowledge, ω-3 PUFAs using the same metabolic pathways and enzymes that metabolize ω-6 PUFAs into arachidonic acid had the opposite effect. The higher proportions of ω-3 PUFAs possess considerably less potent inflammatory effects by producing intercellular signaling molecules such as prostaglandins, leukotrienes, lipoxins, resolvins and protectins, which possess either pro- or anti-inflammatory effects [38–40]. Honda's study also showed that enriching macrophages with EPA or DHA attenuates inflammatory activity initiated by Toll-like receptor 4 activation by reducing tumor necrosis factor-α (TNF-α) and IL-6 secretion [41].

    • Meta-analysis of the efficacy and safety of structured triglyceride lipid emulsions in parenteral nutrition therapy in China

      2019, Clinical Nutrition
      Citation Excerpt :

      Lipid emulsions are an important component of parenteral nutrition (PN), as they not only supply both energy and essential fatty acids, but also contribute to cell membrane structure and function, gene expression, and immune regulation [1–3].

    • Lipidomics in translational research and the clinical significance of lipid-based biomarkers

      2017, Translational Research
      Citation Excerpt :

      Lipid molecules are a subset of the metabolome and serve as ubiquitous and multifunctional metabolites that are integral and essential to many diverse functions on both a cellular and organismal level.1-4 Primary functions of the lipidome include1: compartmentalization of cells and organelles via the formation of membranes2; storage of excess calories to provide a reservoir of energy when needed or to act as the primary energy source for high-energy demand organs (eg, heart)3; regulation of biochemical reactions via influencing the activity of transient and permanent membrane protein interaction; and4 function as a reservoir of bioactive lipids that can be utilized in signaling following agonist-induced hydrolysis or enzymatic/non-enzymatic covalent modifications.1-4 Acting as the boundaries of cells and organelles, lipids are directly exposed to biochemical changes in the intracellular and extracellular milieu and as a result undergo chemical and structural modifications themselves.

    • Structured triglycerides versus physical mixtures of medium- and long-chain triglycerides for parenteral nutrition in surgical or critically ill adult patients: Systematic review and meta-analysis

      2017, Clinical Nutrition
      Citation Excerpt :

      Parenteral nutrition (PN) is indicated in critically ill patients who are malnourished or at risk of malnutrition and have a dysfunctional gastrointestinal (GI)-tract not suitable for adequate enteral feeding [1]. Lipids are an essential component of PN, not only as an energy-dense source of calories within PN formulations but also due to their important metabolic and functional properties, e.g. as building blocks for membrane phospholipids, carriers for fat-soluble vitamins, providers of essential fatty acids, and precursors for important bioactive lipid mediators with the ability to influence inflammation and immunity [2–4]. Triacylglycerols (TGs) consisting of three fatty acids (FA) attached to a glycerol backbone are the primary components of parenteral lipid emulsions.

    View all citing articles on Scopus
    View full text