AbstractOne of the fundamental principles guiding the pharmaceutical quality of parenteral products is to prevent injecting contaminants from microbiological, chemical or physical sources. It is just as difficult to ensure the absence of chemical and particulate contaminants in injectable products as it is to weigh up the microbiological risk. The problem of particulate matter is mainly related to the preparing and administrating of injectable drugs rather than through the contamination of marketed products. Particulate contamination also arises

Studies have shown that infused particles lead to numerous complications such as inflammation or organ dysfunctions in critically ill children. Nevertheless, there is very little data available to evaluate the amount of particulate matter potentially administered to patients, and none with regard to infants. We have investigated the quantity received by these patients during multidrug IV therapies. Two different protocols commonly used in our neonatal intensive care unit (NICU) to manage excessively preterm infants were reproduced in the laboratory and directly connected to a dynamic particle analyser. The particulate matter of infused therapies was measured over 24 h, so that both overall particulate contamination and particle sizes could be determined. No visible particles were observed during drug infusions. Particulate analyses showed a significant number of particles that can reach 85,000 per day, with peaks during discontinuous drug infusions. Moreover, we showed that very large particles of about 60 µm were infused to infants. This study showed that despite very low infusion flow rates, infants may receive a large number of particles during drug infusion, especially in NICUs. Particulate contamination of IV fluids is not without consequences for fragile infants. Preventive solutions could be effective, such as the use of in-line filters.

PurposePlastic materials such as polyurethane (PUR), polyethylene (PE), polypropylene (PP) and polyvinyl chloride (PVC) are widely used in double-lumen extension tubing. The purposes of our study were to 1) compare in vitro drug delivery through the double extension tubes available on the market 2) assess the plastic properties of PUR in infusion devices and their impact on drug delivery.MethodsThe study compared eight double-lumen extension tubes in PUR, co-extruded (PE/PVC) plastic and plasticised PVC from different manufacturers. Isosorbide dinitrate and diazepam were used as model compounds to evaluate their sorption on the internal surface of the infusion device. Control experiments were performed using norepinephrine known not to absorb to plastics. Drug concentrations delivered at the egress of extension tubes were determined over time by an analytical spectrophotometric UV-Vis method. The main characteristics of plastics were also determined.ResultsSignificant differences in the sorption phenomenon were observed among the eight double-lumen extension tubes and between pairs of extension tubes. Mean concentrations of isosorbide dinitrate delivered at the egress of double-lumen extension tubes after a 150-minute infusion (mean values ± standard deviation in percentage of the initial concentrations in the prepared syringes) ranged between 80.53 ± 1.66 (one of the PUR tubes) and 92.84 ± 2.73 (PE/PVC tube). The same parameters measured during diazepam infusion ranged between 48.58 ± 2.88 (one of the PUR tubes) and 85.06 ± 3.94 (PE/PVC tube). The double-lumen extension tubes in PUR were either thermosetting (resin) or thermoplastic according to reference.ConclusionsClinicians must be aware of potential drug interactions with extension tube materials and so must consider their nature as well as the sterilisation method used before selecting an infusion device.

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AbstractThe administration of several intravenous products on the same catheter is a very common situation in neonatology, where the stakes are high and the dangers sometimes unknown to clinicians. A large number of factors are involved in this administration, directly related to the installation of the infusion line. Moreover, the therapeutics used are often limited, and excluding classic “Marketing Authorization”. Some of these products may prove to be incompatible and thus lose their effectiveness, or even generate particles that are likely to be administered to the patient. We must be aware of these risks in order to optimize the prescription and administration of these intravenous products, especially as we treat fragile and immature patients. The aim of this work is to review the literature on the subject for the prescribers of neonatology units.

Interactions between medical device material and the drug itself have been evoked for polyurethane and may lead to underdosing. Polyurethane, sterilization mode, and the crosslinking level of the polymer have an influence on sorption. The aim here is to evaluate the impact of polyurethane conservation time and conditions as well as sterilization mode. Two polyurethane extension tubes were tested, one sterilized by ethylene oxide and the second by gamma radiation. Forced degradation experiments were performed. After 3 and 6 months of incubation, thermal properties, diazepam delivery and cytotoxicity of leachates were assessed. Diazepam delivery differs significantly according to the version of polyurethane. Sterilization however has no impact on diazepam delivery. No cytotoxicity was observed whatever the infusion tube and the aging conditions. In conclusion, sterilization procedures do not induce polyurethane degradation, but high temperature/relative humidity/time storage conditions lead to a slight degradation in polyurethane.

BackgroundCatheter-related bacteremia (CRB) is the most frequent nosocomial infection in neonatal intensive care unit (NICU) patients, especially in very low-birth-weight infants. Administration of injectable drugs in premature newborn infants has many particularities and several types of infusion incidents have been reported. The Edelvaiss® Multiline NEO device is a novel multi-lumen access infusion device adapted to the specificities of infusion in neonatology. This multicenter, randomized, controlled study was therefore designed to determine whether or not Edelvaiss® Multiline NEO reduces the risk of CRB in preterm newborn infants in an NICU.Methods/designThis is a multicenter, randomized, controlled trial, using a cluster-randomized crossover design. Four investigator centers (four clusters) will participate in the study and will be randomized into two groups, corresponding to two different sequences (either the Edelvaiss® Multiline NEO or standard infusion system sequence, then vice versa). A total of 280 patients will be recruited. Infants will be enrolled in the study at the time of placing a single-lumen central venous catheter. Three visits recording specific data are planned in the study protocol. The primary outcome measure is the incidence density (ID) of CRB. For each patient, the total number of catheters and CRB incidents as well as the duration of stay in the NICU will be computed and considered for analysis.DiscussionThe study will provide high-quality evidence to determine whether the Multiline NEO device reduces the risk of CRB in preterm newborns in NICUs or not.Trial registrationClinicalTrials.gov, NCT02633124. Registered on 7 December 2015.Electronic supplementary materialThe online version of this article (10.1186/s13063-019-3218-6) contains supplementary material, which is available to authorized users.