Physical compatibility of insulin aspart, lidocaine, alprostadil and vancomycin with individualised two-in-one parenteral nutrition used in the neonatal intensive care unit

Abstract

OBJECTIVES: Critically ill newborn infants often require simultaneous administration of multiple intravenous (IV) solutions through the same catheter lumen, making compatibility of these solutions crucial in neonatal intensive care units (NICUs). This study aimed to investigate the physical compatibility of insulin aspart, lidocaine, alprostadil and vancomycin with individualised two-in-one parenteral nutrition (PN). METHODS: The study was conducted at the hospital pharmacy's drug compounding facility of the University Medical Centre Utrecht. Two PN formulations were prepared with different electrolyte concentrations (PN1 with high electrolytes and PN2 with low electrolytes), each with either 0% or 30% w/v glucose, resulting in four solutions for testing. Each solution was then mixed with the selected IV drugs in a 1:1 ratio. Compatibility was assessed through visible particle testing, pH measurements and subvisible particle testing at multiple time points (T=0, T=1, T=4 hours). RESULTS: No visible particles were detected in any combinations. However, insulin and lidocaine combinations exceeded the subvisible particle threshold of 6000 particles ≥10 µm per container volume at T=0 hours, with insulin also exceeding the threshold in a specific PN combination at T=4 hours. pH measurements indicated minimal shifts in the PN solutions, suggesting significant buffering capacity. CONCLUSION: Alprostadil and vancomycin IV solutions are physically compatible with two individualised neonatal PN solutions, with high as well as low glucose concentrations. Combinations of PN with lidocaine or insulin form subvisible particles, which could have clinical implications if administered in large volumes over extended periods of time. In clinical scenarios where there is no other option but to administer lidocaine or insulin through the same catheter lumen as PN using a Y-site connector, the use of an in-line filter is advised. Our study adds important compatibility data that can guide clinical practice in NICU settings. However, the broader application of these results requires careful consideration of the unique characteristics of each neonatal PN solution and drug combination.