Compassionate Use of an Intravenous Fat Emulsion Comprised of Soy Oil, Medium Chain Triglycerides, Olive Oil, and Fish Oil for Children With Parenteral Nutrition Induced Liver Injury

H-34444

While fish-oil lipid emulsions have shown a benefit to the treatment of parenteral nutrition (PN)-associated cholestasis, the dose is limited to 1 g/kg/day. Similarly, in early PN-associated cholestasis the dose of soy-based lipid is limited to 1 g/kg/day. Often the calories that are lost from this relative decreased dose of lipids can be provided by adjusting the dextrose content of the PN solution and providing a higher glucose infusion rate. In some cases, this is not tolerated or even with maximizing this strategy, growth is inadequate. Inadequate growth is a direct cause of poor outcomes including poorer neurological outcome, failure to be able to stop mechanical ventilation and poorer growth of their often already damaged intestine. These outcomes can lead to severe disability and death. Therefore, infants receiving only 1 g/kg/day of lipids who are not adequately growing must have a greater intake of lipids to meet their needs for weight, length, and head circumference growth. SMOFlipid (Fresenius Kabi, Bad Homburg, Germany) contains a mixture of 4 different lipid sources: soybean oil providing essential fatty acids, olive oil rich in monounsaturated fatty acids which are less susceptible to lipid peroxidation than polyunsaturated fatty acids, medium-chain triglycerides showing a faster metabolic clearance than long-chain triglycerides, and fish oil for the supply of omega-3 fatty acids. It is safe to give in what is the usual dose for lipid therapy in neonates of 3 g/kg/day, rather than being limited to 1 g/kg/day as we do with cholestatic infants receiving Omegaven or soy lipids. Because this product includes both omega-6 and omega-3 lipids, it provides the benefits of the omega-3s for the liver and provides more than enough omega-6s to meet essential fatty acid requirements. Its use in situations in which growth is inadequate in babies who must be restricted to 1 g/kg/day can be expected to improve their growth and likely markedly increase their chances of both a good neurological outcome and survival. Purpose: We want to find out if this new intravenous fat mixture (SMOFlipid) will help promote good growth while reducing the severity (or seriousness) of liver disease or help put an end to liver disease in infants.

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Inclusion Criteria: * Greater than 14 days old and less than 1 year of age. * Greater than 1.5 kg. * Mild cholestasis, defined as a conjugated bilirubin between 0.5-1.9 mg/dL, or currently receiving Omegaven (fish oil lipid emulsion) with a conjugated bilirubin between 0.0-1.9 mg/dL. * Currently receiving 1 g/kg/day of either Omegaven (H-23365) or soy-based Intralipid (standard therapy) * Evidence of growth of weight, head circumference or length below our standards for post-menstrual age for at least 1 week. * Be expected to require intravenous nutrition for at least an additional 21 days. Exclusion Criteria: * Have a congenitally lethal condition (e.g. Trisomy 13). * Have clinically severe bleeding or clinical liver failure not able to be managed with routine measures. * Have evidence of a viral hepatitis or primary liver disease as the primary etiology of their cholestasis. * Have other health problems such that survival is extremely unlikely even if the infant's cholestasis improves

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2024-05-30