Update on Parenteral Lipids:
Which Patient ? Which Emulsion ? How much ? When ?
Michael Adolph, M.D.
Dept. of Anaesthesiology & Intensive Care, Klinikum Wolfsburg, 38440 Wolfsburg, Germany
phone +49-5361-80-1410, fax +49-5361-80-1624, e-mail: Adolph-Michael@t-online.de
Learning Objectives
 To identify the patients who will benefit from lipid emulsions in a TPN regimen
 To classify available lipid emulsions according to composition and metabolic effects
 To list the differential indications for the currently available lipid emulsions
 To understand principles and practice of the dosage and monitoring of intravenous
lipid emulsions
Introduction
Dietary lipids are efficient fuels for many tissues of the body and can be used to prevent or
correct essential fatty acid deficiency. Lipid emulsions are an important energy source for
all patients requiring TPN because of their high energy density and low osmolarity. During
the past two decades the old concept of only long chain triglycerides containing lipid
emulsions was followed by newer concepts of reducing the high content of n-6 PUFA´s.
The first step in that development was a physical mixture of medium and long chain
triglycerides (MCT/LCT). Meantime this is a well proven concept in TPN regimens of many
different patient types and disease states. A reduced content of n-6 PUFA´s can also be
obtained by using newer preparations based on structured triglycerides or olive oil. A more
promising step in the evolution of lipid emulsions can be seen in including fish oils to a
physical mixture of MCT and LCT.
Lipid Emulsions Containing MCT/LCT
MCT/LCT-containing lipid emulsions have been available on the European market since
1984 and later worldwide. Meantime a great number of working groups have studied the
parenteral application of this physical mixture not only in a clinical environment but also
during long-term home parenteral nutrition (HPN). MCTs have several advantages in
comparison with LCTs 1. Because of their physical and chemical properties, MCTs have
better solubility and are more readily hydrolyzed by lipases. They are more quickly eliminated from the circulation and taken up by peripheral tissues. They are not stored as body
fat but are oxidized more rapidly than LCTs. MCTs are ketogenic, and both medium-chain
fatty acids and ketone bodies are carnitine-independent substrates.
Compared directly with pure LCT emulsions, MCT/LCT emulsions are a more efficient
fuel, put less strain on the liver, and have significantly less impact on the immune system
and RES function. MCT/LCT emulsions appear to be of particular benefit to patients with
systemic inflammatory response syndrome (SIRS) or sepsis because – containing only
half the amount of long-chain triglycerides – they supply a significantly smaller amount of
n-6 fatty acids and hence of the precursors of potentially immunosuppressive prostaglandins 2.
Lipid Emulsions Containing Structured Triglycerides
As an alternative to the physical mixture of MCT and LCT emulsions a mixture of MC and
LC fatty acids can be obtained by interesterifying the different fatty acids to create a mixed
triglyceride molecule called a structured triglyceride (STG) 3. Among STG chemically
defined and randomized STG must be differentiated. Chemically defined STG molecules
may act more efficiently but the costs for the synthesis are very high. This is why most of
the research work in animals and patients was done with randomized STG emulsions.
In 1997 Kruimel et al 4 presented the preliminary results of a study comparing the effect
of randomized STG with a physical MCT/LCT mixture on the nitrogen balance of moderately catabolic patients after insertion of an aortic prosthesis. TPN was infused for 5 days.
Over this period the cumulative nitrogen balance was less negative in the STG group but
an adequate interpretation is difficult before the full publication of the study data. Regarding effects on the mononuclear phagocyte system as studied by use of the 99 m-technetium-sulfur colloid (TSC) clearance technique they found no difference between both
groups 4.
Chambrier et al 5 measured 3-methylhistidine excretion and total urinary nitrogen output
in forty patients, scheduled for abdominal surgery. They were randomized to receive either
STG or a physical MCT/LCT mixture. TPN was started on the day after surgery providing
100% of measured energy expenditure as 50% lipids and 50% glucose and 0.2 g nitrogen
per kg bw and day. There were no significant differences in both outcome variables after 6
days of TPN.
In conclusion, STG have been proven to be as safe as traditional LCT soybean oil emulsions. Compared to LCT, random STG have shown similar advantages as physical
MCT/LCT mixtures. Further studies are necessary, to investigate potential benefits of STG
compared to MCT/LCT in clinical settings.
Lipid Emulsions Containing Olive Oil
The potential of olive oil based emulsions for reduced lipid peroxidation was studied by
several authors yielding conflicting results. From their animal study Dutot et al 6 concluded that olive oil emulsions are a better source of antioxidants and should contribute to
decreased peroxidation. Arborati et al 7 evaluated both the lipid peroxide content and the
peroxidability of fat emulsions under oxidative conditions. While highest values for lipid
peroxide content were found in a 20% soybean emulsion the peroxidability was significantly increased in the soybean/olive-oil mixture. Lowest levels were found in a physical
mixture of MCT/LCT.
Garcia de Lorenzo et al 8 compared the Olive/Soya oil based lipid emulsion with a
physical mixture of MCT/LCT in burned patients. After 6 days of TPN changes in plasma
lipids, haemogram and liver function tests were similar in both groups. No differences
between the two lipid emulsions on patients nutritional status or clinical outcome (ICU and
hospital length of stay) were observed.
Compared to conventional LCT emulsions, olive oil-based lipid emulsions show potential
benefits regarding peroxidation and immune function. However, no clinically relevant outcome data are yet available demonstrating any advantage with regard to MCT/LCT emulsions.
Lipid Emulsions Containing Fish Oil
As reported previously [9], lipid emulsions containing fish oil (n-3 fatty acids) are poor
substrates for lipoprotein lipase (LPL) and tend to accumulate in the circulation. In contrast
to most triglyceride fatty acids, they are taken up by tissues mainly via remnant endocytosis, followed by intracellular triglyceride hydrolysis. Even the addition of n-3 containing triglycerides to classical LCT emulsions inhibits the release of free fatty acids from
the soybean oil emulsion [9]. In contrast, the combination in the same particle of MCT
together with n-3 fatty acid triglycerides appears to completely normalize triglyceride
hydrolysis by LPL [10] and to rapidly produce small remnants enriched with n-3 fatty acids.
In addition, Carpentier et al. [11] obtained evidence that the presence of both MCT and n3 fatty acid triglycerides in remnant particles enhances their uptake by different types of
cells. Not only the alsolute amount of n-3 fatty acids, but the n-6/n-3 fatty acid ratio is
determining the effects of an n-3 enriched lipid emulsion. Conventional soybean
containing lipid emulsions have a n-6/n-3 ratio of approximatly 7:1, the olive / soybean
mixture of 9:1. The recommended ratio of 4:1 to 2:1 for serverely ill patients [12, 13] is
based on the requirements of healthy people (below 5:1 [14]) and takes into account the
enhanced omega-3-fatty acid requirements of ill patients in respect to lowering the risk of
an overwhelming systemic inflammatory response in hyperinflammatory stress situations.
In 40 patients undergoing major intestinal surgery Wachtler et al. [15] analyzed the effect
of TPN with a physical MCT/LCT mixture plus n-3 fatty acid triglcerides versus TPN with a
physical MCT/LCT micture alone on the release of leukotrienes from whole blood leucocytes as well as circulating cytokines. In the n-3 supplemented group they observed a
significant increase in 5-series leukotrienes and a decrease in the 4-series leukotrienes as
an indicator of an attenuated inflammatory reaction. In contrast to interleukin-1, interleukin-6, and interleukin-10, the systemic levels of tumor necrosis factor- were postoperatively decreased in the n-3 supplemented group.
n-3 fatty acids may also modulate regional blood flow and possibly prevent intestinal
ischemia. Pscheidl et al. [16] could demonstrate in a low-dose endotoxin rat model that
diets enriched with fish oil abolish the endotoxin-induced decrease of nutritive blood flow
to the gut and ameliorate the bacterial defense of the splanchnic region. The lower count
of viable bacteria in the fish oil groups was more related to an improved killing of translocated bacteria than a reduction of the translocation rate.
Gadek et al. [17] could demonstrate that in patients with ARDS artificial nutrition for at
least 4–7 days with a enteral diet supplemented with eicosapentaenoic acid (EPA), -linolenic acid (GLA), and antioxidants was superior to a control diet in terms of reduced pulmonary neutrophil recruitment and inflammation, improved oygenation, reduced time on
the ventilator and stay in the ICU, and reduced morbidity as defined by the number of patients newly developing organ failure.
However, not only n-6 but also n-3 polyunsaturated fatty acids are substrates for lipid peroxidation and inadequate balance by antioxidants may jeopardize their beneficial effects.
Therefore a well balanced enrichment of this new generation of lipid emulsion with -tocopherol is strongly recommended [18].
Lipid Emulsions: When? How much?
In clinical practice, lipids are suitable energy sources whenever TPN is indicated. Isolated
organ failure per se is not a contraindication to the parenteral application of lipid emulsions. However, in all cases of impaired tissue blood flow and peripheral oxygen deficiency, e.g. as in shock, any type of TPN is contraindicated including the infusion of parenteral lipids. The patient should be hemodynamically stable before any form of nutrition is
resumed. Following massive blood transfusions or in the presence of severe coagulation
disorders, lipid infusion should be withheld temporarily. Caution should be exercised in
primary lipid metabolism disorders, and lipid emulsions should be given only to provide
essential fatty acids. In general, the dosage for lipid emulsions is between 0.5 and 1.5
g/kg bw/day. The calculated amount of lipids should be infused over at least 12 h per day,
and during critical metabolic situations, a 24 h continuous infusion is strongly recommended. The ratio of fat calories to carbohydrate calories should be similar to that of a
normal oral diet, i.e. one-third of calories should be provided as fat and two-thirds as carbohydrate. However, in times of critical illness and sepsis, when glucose intolerance is
dominant and carbohydrate should not be given in excess of 3 g/kg bw/day, the proportion
of infused fat can be increased to 1 : 1. The parenteral application of lipid emulsions
should be increased in a stepwise manner with concomitant monitoring to ensure stable
values of serum tiglycerides of no more than 3 – 4 mmol/l.
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