Co-administration of drugs with parenteral nutrition in the neonatal intensive care unit—physical compatibility between three components

Abstract

There is a lack of compatibility data for intravenous therapy to neonatal intensive care unit (NICU) patients, and the purpose of this study was to contribute with documented physical compatibility data to ensure safe co-administration. We selected Numeta G13E, the 3-in-1 parenteral nutrition (PN) used at our NICU, together with the frequently used drugs morphine, dopamine and cefotaxime in two- but also three-component combinations. Incompatibility may lead to particle formation (precipitation) and oil-droplet growth (emulsion destabilisation), both which are undesirable and pose a safety risk to already unstable patients. We assessed potential particle formation of three mixing ratios for each combination (always including 1 + 1 ratio) using light obscuration, turbidity and pH measurements combined with visual inspection by focused Tyndall beam. Potential droplet-growth and emulsion destabilisation was assessed by estimating PFAT5 from droplet size measurements and counts, mean droplet diameter and polydispersity index from dynamic light scattering, and pH measurements. Mixed samples were always compared to unmixed controls to capture changes as a result of mixing and samples were analysed directly after mixing and after 4 h to simulate long contact time. None of the samples showed any sign of precipitation, neither in the drug-drug nor in the two- or three-component mixture with PN. Neither did we detect any form of emulsion destabilisation.Conclusion: Dopamine, morphine and cefotaxime were found to be compatible with NumetaG13E, and it is safe to co-administer these drugs together with this PN in NICU patients. What is Known:• The need for co-administration of drugs and complex PN admixtures occurs frequently in NICU due to limited venous access.• Available compatibility data are scarce and for combinations of more than two components non-existent. What is New:• Here we report physical compatibility data of two- as well as three-component combinations of frequently used NICU drugs and a 3-in-1 PN admixture.• Co-administration of Numeta G13E with dopamine and morphine, but also with morphine and cefotaxime is safe in NICU.

Frequently acquired drugs in neonatal intensive care and their physical compatibility

“…In addition, cefotaxime and vancomycin have recently been studied. 14 , 15 Therefore, the two penicillins, ampicillin and benzylpenicillin, were selected together with the antifungal drug fluconazole. Finally, the test candidate from group N was morphine.…”

“…Fentanyl, the top candidate in this group, was recently studied by our group. 15 Even though morphine also has recently been, 14 there are limited compatibility data on morphine hydrochloride. Morphine is a versatile drug that is used in combination with all the selected drugs and was therefore tested in combination with each of the other drugs.…”

“… 10 One exception was the study by Nilsson et al that analysed the compatibility of dopamine, morphine and cefotaxime at clinically relevant mixing ratios using a battery of compatibility tests and concluded that they are compatible, both with each other and with a neonatal parenteral nutrition admixture. 14 The same parenteral nutrition was also found to be compatible with fentanyl, paracetamol and vancomycin. 15 Another exception was the study by Staven et al where two neonatal parenteral nutrition products were reported to precipitate when mixed with ampicillin, fosphenytoin and furosemide.…”

Exploring a case of incompatibility in a complex regimen containing Plasma‐Lyte 148 in the pediatric intensive care

“…A number of well‐established methods was used to scrutinize for any sign of particle formation in the mixed samples. 5 , 6 , 15 The smallest capillaries in the body have a diameter of approximately 5 μm. Particles in this range are sub‐visible and cannot be detected by visual examination.…”

“…Co‐infusion of incompatible drugs and fluids via the same catheter line and/or lumen may result in the formation of solid particles, that is, drug precipitates. 5 , 6 These precipitates may clot the i.v.‐catheter line and find their way into organs. 7 , 8 , 9 There have been reports of fatal outcome in children due to infusion of solid particles.…”