ABSTRACT
Intravenous drug incompatibilities are a common cause of medical errors, contributing to ineffective therapy and even life-threatening events. The co-administration of drugs must always be supported by studies confirming compatibility and thus guarantee the therapy's safety. Particular attention should be paid to the possible incompatibilities or degradation of intravenous cephalosporins in different infusion regimens since the administration of drugs with inadequate quality may cause treatment failure. Therefore, an appropriate stability test should be performed. The study aimed to present various aspects of the stability and compatibility of five cephalosporins: cefepime (CFE), cefuroxime (CFU), ceftriaxone (CFX), ceftazidime (CFZ), and cefazoline (CFL). The degradation studies in parenteral infusion fluids and PN admixtures were conducted for CFE and CFU. The interactions between CFX or CFZ and PN admixtures, as well as the compatibility of CFL with five commercial parenteral nutrition (PN) admixtures, were investigated. The content of CFX and CFZ in PN admixture after 24 h was >90%. CFL administered simultaneously with PN admixture by the same infusion set using Y-site was compatible only with Nutriflex Lipid Special. CFE and CFU were stable in all tested infusion fluids for a minimum of 48 h and decomposed in PN admixtures during storage.
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.
ABSTRACT
A serious problem in everyday clinical practice is the co-administration of drugs using the same infusion line. Potential complications of co-administration of incompatible drugs include precipitation in the infusion line or central venous catheter leading to its occlusion. Administration of precipitate and large lipid droplets into the venous system may lead to the embolization of capillaries and local or systemic inflammatory reactions, with the consequences of venous thrombosis, chronic venous insufficiency, and even pulmonary embolism. The co-administration of drugs must always be confirmed and clearly defined. The study aimed to determine the interaction between colistin (COL) in the dose used during intermittent hemodialysis and five different ready-to-use PN admixtures (PN) (Kabiven, Smofkabiven, Olimel N9E, Nutriflex Lipid Special, and Nutriflex Omega Special). COL-PN compatibilities were tested by comparing physicochemical properties (pH, zeta potential, lipid emulsion particle size) of COL and PN at three time points: immediately after sample preparation, after ten minutes, and after four hours. No changes in the visual inspection were observed. Both PN without COL and COL-PN samples remained white, homogeneous oil-in-water emulsions with no signs of phase separation, precipitation, or color change. There were no significant changes in pH, and the mean droplet diameter remained below the acceptance limit of 500 nm. The zeta potential and osmolality of COL-PN samples ranged from -21.4 to -7.22 mV and from 567 to 1304 mOsm/kg, respectively. The COL does not influence the physical stability of studied PN admixtures. The co-infusion of COL with Kabiven, Nutriflex Lipid Special, Olimel N9E, Nutriflex Omega Special, and Smofkabiven is possible in the dose used during intermittent hemodialysis.
ABSTRACT
BACKGROUND & AIMS: A co-infusion of parenteral nutrition (PN) and other drugs is often necessary in patients with a limited number of vascular access sites. This practice increases the risk of interaction between drugs and PN admixtures that may be manifested as drug precipitation or lipid emulsion destabilization. The present study aimed to determine the compatibility between vancomycin (VMC) and five ready-to-use PN admixtures utilized worldwide (Kabiven, Nutriflex Lipid Special, Olimel N9E, Nutriflex Omega Special, and Smofkabiven) in order to assess the possibility of their co-administration via Y-sites. METHODS: VMC and PN admixtures were mixed at three volume ratios (1:1, 1.5:1, and 3:1) and potential interactions were examined using visual inspection, pH and osmolality measurements, as well as particle size and zeta potential determination. The analyses were conducted immediately after sample preparation and after 4 h of storage. RESULTS: The PN admixtures were characterized by the pH in the range from 5.44 to 6.23, the osmolality in the range from 1169 ± 3 mOsm/kg H2O to 1929 ± 6 mOsm/kg H2O. The zeta potential of the PN admixtures was between -12.97 ± 0.86 mV and -4.55 ± 0.45 mV. The particle size, expressed as mean droplet diameter (MDD) ranged from 226.8 ± 4.2 nm to 281.6 ± 6.3 nm. The addition of VMC to PN admixtures caused a decrease in the pH, osmolality, and zeta potential. The MDD values for all samples were below 500 nm, except VMC-Olimel N9E at the volume ratio 1:1 (v/v), for which MDD = 805 nm. The presence of lipid particles exceeded the size of 4000 nm was observed for VMC-Olimel N9E and VMC-Smofkabiven. CONCLUSIONS: We suggest that a simultaneous administration of VMC with PN admixtures containing olive oil should be avoided. As we established, this type of emulsion is less stable and tends to form agglomerates when combined with VMC. However, as demonstrated in our study, when it is necessary to co-administer VMC with PN admixtures, this is possible with Kabiven, Nutriflex Lipid Special, and Nutriflex Omega Special at volume ratios of 1:1, 1.5:1, and 3:1.
