Toward Safe Pharmacotherapy: The Interplay between Meropenem and Parenteral Nutrition Admixtures

Abstract

Simultaneous administration of parenteral nutrition (PN) admixtures with intravenous antibiotics is a common clinical problem. Coadministration of drugs incompatible with PN admixture may affect its stability, especially in the context of lipid droplet size, which is a crucial parameter for patient safety. In the present study, we investigate the in vitro compatibility of meropenem (Meropenem 1000, MPM) with five commercial PN admixtures used worldwide: Kabiven, Olimel N9E, Nutriflex Lipid Special, Nutriflex Omega Special, and SmofKabiven. The appropriate volumetric ratios, reflecting their clinical practice ratios, were used to prepare the MPM–PN admixture samples. Physicochemical properties of MPM–PN admixtures samples were determined upon preparation and after four hours of storage. The pH changes for all MPM–PN admixtures samples did not exceed the assumed level of acceptability and ranged from 6.41 to 7.42. After four hours of storage, the osmolarity changes were ±3%, except MPM–Olimel N9E samples, for which differences from 7% to 11% were observed. The adopted level of acceptability of changes in zeta potential after four hours of storage (±3 mV) was met for MPM–Kabiven, MPM–Nutriflex Lipid Special, and MPM–Nutriflex Omega Special. The mean droplet diameter for all samples was below 500 nm. However, only in the case of Nutriflex Lipid Special and Nutriflex Omega Special, the addition of MPM did not cause the formation of the second fraction of lipid droplets. The coadministration of MPM via Y-site with Kabiven, Olimel N9E, and Smofkabiven should be avoided due to osmolarity fluctuations (MPM–Olimel), significant differences in zeta potential (MPM–Olimel, MPM–Smofkabiven), and the presence of the second fraction of lipid droplets >1000 nm (MPM–Kabiven, MPM–Olimel, and MPM–Smofkabiven). The assumed acceptance criteria for MPM compatibility of MPM with PN admixtures were met only for Nutriflex Lipid Special and Nutriflex Omega Special in 1:1, 2:1, and 4:1 volume ratios.

Sodium Valproate Incompatibility with Parenteral Nutrition Admixtures—A Risk to Patient Safety: An In Vitro Evaluation Study

“…Until now, no official compendium or harmonized methodology has been established to evaluate PNA stability. Based on the research data and our own experience, we used different analytical methods which allowed us to detect changes in the physicochemical properties of VPA-RTU samples [15][16][17][18]31,32,[39][40][41][42][43][44][45][46]. Despite the duration of the VPA infusion of approximately a few hours and of the PNA from 16 to 24 h, the real-time contact in a common line of Y-site connector lasted only a few minutes.…”

“…The pH of the PNA should not change during the test (4 h) by 0.2, and the change after mixing with the drug should not be greater than the ΔpH = 0.5 [18,31].…”

“…A total of 100.0 µL of sample was transferred into an OSMO-KRIO cuvette, and then analyzed. The acceptance limit for osmolality changes was set as <5% [16,31].…”

Stability and Compatibility Aspects of Drugs: The Case of Selected Cephalosporins

“…The compatibility of five different ready-to-use PN admixtures (Kabiven, Smofkabiven, Olimel, Nutriflex LS, and Nutriflex OS) and CFL solution in three different volume ratios of 1:1, 2:1, and 4:1 was tested. The procedure of sample preparation was similar to our previous investigations concerned with the compatibility studies of PN admixtures and meropenem, vancomycin, or colistin [ 11 , 33 , 61 ]. Briefly, PN admixtures were activated and supplemented in aseptic conditions.…”

“…The first one is the addition of the reconstituted drug to infusion fluids to store for a longer time [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ] or, in the case of PN admixture, the use of such medium as a drug carrier [ 27 , 28 , 29 , 30 , 31 , 32 ]. The second study protocol assumes administering two infusion drugs through the same infusion set using a Y-site connector [ 11 , 33 , 34 , 35 , 36 , 37 ]. In this case, the contact time between drugs is very short and limited only to the common part of the infusion line.…”