There is increasing interest to administer ibuprofen as a continuous infusion instead of a traditional bolus for treating Patent Ductus Arteriosus (PDA). However, its compatibility data with commonly used drugs in the neonatal period, including parenteral nutrition (PN) and lipids is unavailable. The aim is to determine the compatibility of intravenous ibuprofen lysine with various ANZNN parenteral nutrition consensus group standard neonatal PN formulations and lipids. The PN and lipid solutions used in a tertiary neonatal unit were obtained. These included a Starter, Standard Preterm and low carbohydrate PN, and IV SMOF lipid admixture (SMOFLipid 20% 15 mL; Vitalipid N infant 4 mL, Soluvit N 1 mL) plus vitamin mixtures. 10% glucose was used as a control. 1:1 mixtures of different concentrations (1.25 to 5mg/mL) of ibuprofen lysine and each of the PN/glucose/lipid formulations were made. Samples were taken at hourly intervals for a total of 4 hours and tested for both physical (visual assessment, pH and microscopy) and chemical compatibility (High Performance Liquid Chromatography analysis). Zeta potential and particle diameter were measured for SMOF lipid admixture and ibuprofen combination to assess emulsion stability. 24 hour stability of ibuprofen dilution in 5 mL BD Luer-lok polypropylene syringes at 25°C was also assessed. Most PN formed opaque solutions when mixed with ibuprofen 2.5 and 5mg/mL solutions. However, ibuprofen dilution of 1.25mg/mL produced clear, colourless solutions with no microscopic particles when mixed with all PN/glucose/lipid formulations tested. Ibuprofen was chemically stable with all PN and SMOF lipid admixture, for a period of 4 hours. The zeta potential and particle diameter were within acceptable limits. Ibuprofen lysine was stable over 24 hours in Luer-lok polypropylene syringes. Ibuprofen 1.25mg/mL is physically and chemically compatible with 10% glucose, starter PN, standard preterm and low carbohydrate PN, and SMOF lipid admixture plus vitamins for a period of four hours, which is the maximum time they could be in an admixture during a continuous infusion.

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The use of albumin infusions in neonates remains controversial. Hypoalbuminaemia is associated with necrotising enterocolitis and lung disease; however, correction of low serum albumin does not demonstrably improve neonatal morbidity or mortality.1 Despite this, albumin is widely used in neonatal intensive care. Although commonly used, there is no clear guidance as to the most appropriate method of administration. Previous clinical trials have either administered the total dose of albumin as a separate side-line over a period of 1-2 h, or by adding it to parenteral nutrition and administering the total dose over 24 h.1 The latter approach offers the theoretical advantage of avoiding a rapid administration of albumin, reducing the potential risk of volume retention which can result in fluid overload and associated complications such as pulmonary oedema. For this reason, within our neonatal unit, when albumin is required it is often added to parenteral nutrition solutions (at a dose of 1-2 g/kg/day) prepared by an on-site sterile production service. Our routine practice is to administer parenteral nutrition via a 0.2 micron in-line filter (PALL Posidyne NEO96, Pall Corporation, Port Washington, WI, USA). However, there is no data on the extent of albumin capture by this type of filter.We performed an in vitro experiment to investigate the extent of albumin capture by the in-line filter during infusion of parenteral nutrition. We added 1.5 mL of 20% albumin to 28.5 mL of parenteral nutrition solution (Standard Preterm solution, Baxter Australia, Old Toongabbie, NSW, Australia) in a syringe resulting in a calculated albumin concentration of 10 mg/mL. We then primed standard lines and infused the solution at 4 mL/h for 6 h. This approach mimicked the concentration of albumin in parenteral nutrition solution in a clinical scenario where 1 g/kg/day of albumin is delivered in 96 mL/kg/day of total fluid to a 1 kg baby. Samples for albumin analysis were collected prior to connection to the PALL filter, and every 60 min during the infusion period. Albumin analysis was undertaken using the bromocresol purple (BCP) method on a Roche Cobas c702 analyser (Roche Diagnostics, Mannheim, Germany), which has a validated measuring range of 2-100 g/L.The baseline albumin concentration was 9.4 mg/mL, and at 6 h the level was 9.7 mg/mL. Concentrations at all time points varied by less than 6%, within the normal range of assay variability.The results show that albumin was not filtered out of solution by the in-line filter under the study conditions, demonstrating that albumin passes freely through this style of filter at therapeutic concentrations in combination with parenteral nutrition.