Intravenous Lipid Emulsions

P. C. Calder, D. L. Waitzberg, B. Koletzko

• Verlag: S. Karger
• Jahr: 2014
• ISBN:
  9783318027532
• Thema: Medicine
• Thema: Perinatology & Neonatology

Lipids have been in clinical use as components of intravenous nutrition for over 50 years. Over the last 15 years, new and improved lipids that include olive oil and/or fish oil have replaced the more traditional ones. These new lipids offer the opportunity to deliver high amounts of fatty acids and possess different functional properties: in particular, they can influence inflammatory processes, immune responses and hepatic metabolism. This book brings together articles written by leading international authorities in the area of intravenous lipids. Contributions discuss the latest findings in the field, ranging from pre-clinical research to the most recent clinical trials. Lipid functionality and utility in pediatric, adult surgical and critically ill patients are covered, as is the use of lipids in long-term home parenteral nutrition. Addressing a broad spectrum of topics, this publication provides a wealth of information for basic scientists, clinical researchers and clinical practitioners alike.

Calder PC, Waitzberg DL, Koletzko B (eds): Intravenous Lipid Emulsions.
World Rev Nutr Diet. Basel, Karger, 2015, vol 112, pp 90-114 (DOI: 10.1159/000365604)

______________________

Intestinal Failure-Associated Liver Disease and the Use of Fish Oil-Based Lipid Emulsions

Olivier J. Goulet

Department of Pediatric Gastroenterology, Hepatology and Nutrition, Intestinal Failure Rehabilitation Center, National Reference Centre for Rare Digestive Diseases, Hospital Necker-Enfants Malades, University of Paris-Descartes, Paris, France

______________________

Abstract

Intestinal failure (IF) is caused by the critical reduction of functional gut mass below the minimal amount necessary for adequate digestion and absorption to satisfy body nutrient and fluid requirements for maintenance in adults and growth in children. The advent of parenteral nutrition (PN) resulted in a dramatic improvement in life expectancy of patients suffering IF, but it has its own complications, such as catheter related sepsis. In pediatric patients suffering IF, intraluminal intestinal bacterial overgrowth may cause bacterial translocation and subsequent cholestasis and liver fibrosis. With our current understanding of the genesis of intestinal failure associated liver disease (IFALD), it should be prevented or at least early recognized and treated especially in patients experiencing pre-maturity and/or sepsis. Targeting harmful cytokine responses can be expected to reduce the severity and frequency of IFALD. In that view, prevention of sepsis, appropriate management of enteral feeding, prevention and treatment of intestinal bacterial overgrowth and the effects of fish oil, as providing omega-3 fatty with anti-inflammatory effects, are promising in avoiding or reversing cholestasis. This chapter aims to review both IF and PN related factors of liver disease with special emphasize on inflammation as cause of liver injury and on the use of fish oil based lipid emulsions as a provision of both alpha-tocopherol (200 g/l of 20% emulsion), as anti-oxidant agent and long-chain PUFAs.

© 2015 S. Karger AG, Basel

Introduction

‘Intestinal failure’ (IF) is caused by the critical reduction of functional gut mass below the minimal amount necessary for adequate digestion and absorption to satisfy body nutrient and fluid requirements for maintenance in adults and growth in children [1]. The advent of parenteral nutrition (PN) resulted in a dramatic improvement in the life expectancy of patients suffering from IF, especially for situations of IF occurring in the neonatal period [1]. IF is related to a variety of primary digestive diseases and may be total or partial and permanent or provisional, depending on the cause. PN has improved the outcome after neonatal surgery for congenital abnormalities of the GI tract, including subsequent short bowel syndrome (SBS) or severe motility disorders such as extensive aganglionosis or chronic intestinal pseudo-obstruction [2, 3]. Moreover, PN has made the emergence and diagnosis of rare congenital digestive diseases possible, especially those involving the development of the intestinal mucosa [4].

Due to technical refinements and steady advances in the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients, PN has become a safe feeding technique and continues to play an important role in patient management. However, some complications, such as catheter-related sepsis (CRS) and liver disease (LD), continue at high incidence, particularly in neonates and infants during even a short course of PN [5-7]. Moreover, IF that requires long-term PN may be associated with various complications, including venous thrombosis, growth failure, metabolic disorders, and bone disease. Cholestatic liver disease (CLD) with the risk of fatal outcome from end-stage liver cirrhosis was rapidly identified as one of the limiting factors of long-term IF management and might lead to the so called ‘nutritional failure’, which is considered a major indication for intestinal transplantation (ITx) or combined liver-intestine transplantation [3].

When assessing CLD, factors related to IF itself, those related to septic complications and PN-related factors should always be considered separately. This makes wording very controversial when considering CLD that occurs during PN in children suffering IF that is complicated by sepsis. There is no doubt that CLD is multifactorial. The term “IF-associated liver disease’ (IFALD) seems more adapted than the term ‘parenteral nutrition-associated liver disease’ [8, 9]. In the past, PN itself was thought to be the main cause of LD in relation to inappropriate intake of amino acid solutions, deficiency in macro- and micronutrients or overload with potentially toxic components such as aluminium, iron or manganese [10-13]. Extensive literature, including reviews and textbook chapters, has extensively listed the hypothetical factors of the so-called ‘parenteral nutrition-associated liver disease’ [14, 15]. Today, PN mixtures may be considered as very safe if they are delivered appropriately according to guidelines [16]. Interestingly, clinical data on infants with SBS focused on intravenous lipid emulsions (ILEs) as an important factor of CLD [17], and this will be discussed in this chapter. It is important to note that children demonstrate predominant cholestasis and more rapid progression to fibrosis and end-stage LD, while steatosis is the principal lesion in adults. In patients with SBS, liver dysfunction impairs the intestinal adaptation process, which results in an even more prolonged need for PN. A series of paediatric patients with SBS who required isolated liver grafts for SBS with the potential for adaptation, were reported [18, 19].

Thus, both treatment and prevention of IFALD have the possibility to significantly reduce the need for liver transplantation that is either isolated or combined with the intestine and may enhance the outcome of children with SBS. It is crucial to recognise patients who are at risk for developing LD early on [20-23]. In the scope of this chapter, I will deal with the setting of long-lasting partial or total IF requiring long-term PN. However, some situations, such as prematurity, are not primarily related to IF and/or digestive disease, making analysis and recommendations sometimes difficult for this age group. Indeed, what might be true for infants and children should be nuanced and adapted for premature babies. Most of the data that will be reviewed in this chapter involve infants and children.

Definition and Pathological Expression of Liver Disease

IFALD may appear at any stage of IF management and is defined clinically or biologically. However the diagnostic criteria for IFALD remain debated. The onset of clinical jaundice in a child within a few weeks after starting PN or during the course of long-term PN has been proposed, and this is a late-onset criterion compared to biological changes. Clinical jaundice represents a major disturbance of liver function and occurs after protracted and serious effects on hepatic structure and function have occurred. One of the earliest indications of IFALD is an elevation in alkaline phosphatase or gamma glutamyl transferase within 7-14 days of starting PN. Increased plasma levels of transaminases are commonly observed at the onset of PN, especially in neonates and intensive care unit (ICU) patients, and elevation of these levels to greater than 1.5 times the upper limit of the reference range for at least 2 weeks in the absence of another cause (e.g. drug-induced disease, viral hepatitis, biliary obstruction, metabolic disorder) may be relevant [14, 15]. The hepatic transaminases become elevated to a lesser degree after 2-4 weeks, and thereafter, the liver function tests may stabilise to within the normal range unless an event such as surgery or a catheter infection occurs. The next significant alteration in liver biochemistry is a rise in the conjugated bilirubin concentration. Elevated plasma bilirubin over 50, 70, 100 and 200 μmol/l (equivalent to 3, 4, 6, and 12 mg/dl) is recognised as the criterion for defining IFALD with good sensitivity and specificity. Finally, the most relevant assessment is based on liver biopsy (LB), which is not performed routinely. There is no current recommendation for performing systematic LB, except when small bowel transplantation is discussed. Histopathological expression of LD includes steatosis, cholestasis and fibrosis with various degrees of portal inflammation. In some cases of severe, worsening cholestasis and progressive bil...