Elsevier

Clinical Nutrition

Volume 32, Issue 2, April 2013, Pages 224-231
Clinical Nutrition

Original article
Four-week parenteral nutrition using a third generation lipid emulsion (SMOFlipid) – A double-blind, randomised, multicentre study in adults

https://doi.org/10.1016/j.clnu.2012.06.011Get rights and content

Summary

Precis

The aim of this study was to evaluate the safety and tolerance of a soybean/MCT/olive/fish oil emulsion in intestinal failure patients on long-term parenteral nutrition. 73 patients took part in a randomized, double-blind, multi-centre study. The study demonstrates that the lipid emulsion containing four different types of oils is safe and well tolerated in long-term PN.

Background & aim

Long-term safety and efficacy of a lipid emulsion containing soybean oil, medium-chain triglycerides (MCT), olive oil and fish oil and enriched in vitamin E have not yet been evaluated in adult patients requiring long-term parenteral nutrition (PN).

Methods

Randomised, controlled, double-blind, multicentre study in 73 patients with stable intestinal failure, requiring PN with either soybean/MCT/olive/fish emulsion (SMOFlipid, n = 34) or soybean emulsion (Intralipid, control n = 39) for 4 weeks. Safety and tolerance were monitored with standard clinical laboratory parameters, adverse events (AEs, according to the Common Terminology Criteria for Adverse Events (CTCAE) classification v 3.0) and vital signs. Fatty acid pattern in red blood cell phospholipids and plasma lipoproteins, serum Vitamin E, Interleukin (IL)-6, and soluble tumour necrosis (s-TNF)-receptor(R)II were also evaluated.

Results

Mean concentrations of alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin, whilst remaining within the reference range, were significantly lower with soybean/MCT/olive/fish (SMOF) oil emulsion after the treatment period compared to control. Eicosapentaenoic acid, docosahexaenoic acid and n−3/n−6 fatty acid ratio increased in the SMOF group, while they remained unchanged in the control in plasma and RBC. Serum α-tocopherol concentrations significantly increased in the study group compared to control (p = 0.0004). IL-6 and sTNF-RII levels did not change during the study period. Grade 4 (serious) adverse events occurred in 2 SMOF patients and in 8 control patients (p = 0.03).

Conclusions

Soybean/MCT/olive/fish emulsion was safe and well tolerated over 4 weeks and leads to positive change in fatty acids profile.

Introduction

Intravenous lipid emulsions are an essential component of parenteral nutrition (PN) regimens, representing a major source of energy and essential fatty acids (FAs).1 Intralipid, the first commercially available lipid emulsion2 is based on soybean oil and characterized by a high content of essential long-chain polyunsaturated fatty acids (LC-PUFA), linoleic (LA, n−6; 52–54%) and α-linolenic (ALA, n−3; 7–9%) acid.3 Intralipid has proved to be safe and well tolerated in a wide range of clinical conditions and is used as the standard lipid emulsion.3, 4, 5, 6 However, because of the high supply of LA, alternative lipid emulsions were developed by partially replacing soybean oil with other lipids such as medium-chain triglycerides (MCT), olive oil and fish oil.5, 6, 7

MCT are rapidly cleared from the bloodstream and are less susceptible to lipid peroxidation than PUFA.7, 8, 9, 10 Olive oil is rich in the monounsaturated fatty acid (MUFA) oleic acid, which due to its chemical structure is less prone to lipid peroxidation than PUFA.11 Fish oil contains the n−3 LC-PUFA eicosapentaenoic acid (EPA, C20:5, n−3) and docosahexaenoic acid (DHA, C22:6, n−3). Due to their favourable immunomodulatory and anti-inflammatory properties, provision of EPA and DHA has been considered to be of benefit in patients at risk of inflammation and sepsis.12, 13, 14 Consequently, supplementation of n−3 FA from fish oil has been recommended according to the European Society of Clinical Nutrition and Metabolisms' (ESPEN) guidelines on PN for surgical (Grade C)15 and critically ill patients (Grade B).16

A lipid emulsion containing a physical mixture of Soybean oil, MCT, Olive oil and Fish oil and enriched in vitamin E (SMOFlipid, Fresenius Kabi, Bad Homburg, Germany) has shown safety and tolerance in surgical patients and premature neonates.17, 18, 19, 20, 21 In all of these studies, the duration of PN with this mixed type emulsion has been limited to periods up to 14 days. Safety and clinical efficiency of PN with soybean/MCT/olive/fish oil emulsion have been demonstrated in children on long term home PN.22 First beneficial effects of SMOF with respect to elevated bilirubin levels were reported in infants and children with intestinal failure associated liver disease (IFALD) or cholestasis on long-term PN.23, 24 Nevertheless, clinical evidence on long-term application of this lipid emulsion in adults is still needed.

The aim of the present study was to assess safety and tolerance of a soybean/MCT/olive/fish oil emulsion in comparison to a soybean oil based lipid emulsion in adult patients requiring long-term PN. Additional objectives were the influence of the fatty acid composition on liver function parameters, inflammation process, fatty acid patterns in plasma lipoproteins and red blood cell (RBC) phospholipids, and on antioxidant status.

Section snippets

Experimental design and treatment

The study was a randomized, controlled, double-blind, multi-centre study performed in 11 centres in 7 countries: Australia (2 centres), Denmark (2 centres), France (2 centres), Israel (1 centre), Netherlands (1 centre), Poland (1 centre) and United Kingdom (2 centres).

Between October 2007 and October 2008 75 patients were randomised, and 73 in- and out-patients who received at least one dose of the study or control drug were included in the study and formed the ITT population.

Eligible patients

Patients and diagnoses

In total, 75 patients were randomized in 11 centres. Two patients did not receive any dose of the study admixture, yielding an intention-to-treat (ITT) population of 73 patients, 34 patients in the SMOF group and 39 patients in the control group (Fig. 1). At baseline, groups were comparable with regard to most demographic criteria, but patients in the soybean oil group were significantly younger than the patients receiving SMOF (53.2 vs. 45.2 years, p = 0.02) (Table 2). The most frequent

Discussion

Patients on long-term PN are at risk of complications, such as catheter-related sepsis, metabolic disorders, metabolic bone disease and liver disorder.1 Intestinal failure associated liver disease (IFALD) represents a major limitation for long-term parenteral nutrition management, and may result in cirrhosis and the need for liver transplantation.26 Amongst a variety of factors, long-term use of intravenous lipid emulsions rich in n−6 FAs especially provided at a dose of >1 g fat/kg BW/d has

Conclusion

The results of this study confirmed that a mixed lipid emulsion containing soybean oil, MCT, olive oil and fish oil was safe and well tolerated in a large group of intestinal failure patients requiring parenteral nutrition for 4 weeks. Infusion of the mixed lipid emulsion was effective in modifying the fatty acid composition of both plasma and cellular lipids, with a desirable reduction in n−6/n−3-FA ratio. Furthermore, improvements in parameters of liver function and cholestasis as well as in

Conflict of interest

The authors hereby declare that the article is original, is not under consideration for publication anywhere else and has not been previously published. Moreover, the authors declare no potential or actual personal, political or financial interest in the material, information or techniques described in the paper.

Statement of authorship

Authors state that she/he has made substantial contributions and final approval of the conceptions, drafting, and final version of the manuscript entitled: Long-term parenteral nutrition with a third generation lipid emulsion (SMOFlipid) – a double-blind, randomized, multicentre study in adults.

Acknowledgements

Stanislaw Klek contributed to the data analysis, interpretation and writing of the manuscript. Jon Shaffer was the principle investigator and critically revised the intellectual content of the study and the manuscript. Pierre Singer was responsible for the data collection and critical revision of the intellectual content of the study. All the authors carried out the study and were responsible for the data collection.

The authors wish to express their gratitude to Doctor Claude Wolf for carrying

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