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Insulin is a frequently prescribed drug in hospitals and is usually administered by syringe pumps with an extension line which can be made of various materials. Two insulin solutions were studied: an insulin analogue, Novorapid® which contains insulin aspart and two phenolic preservatives (e.g. phenol and metacresol) and Umuline rapide® with human insulin and metacresol as preservative. Some studies have indicated interactions between insulin, polyvinyl chloride (PVC) and polyethylene (PE). The aim of this work was to study such interactions between Novorapid® or Umuline rapide® and infusion extension line materials (PVC, PE and coextruded (PE/PVC)). Insulin solution at 1 IU/mL was infused at 2 mL/h over 24 hours with 16 different extension lines (8 in PVC, 3 in PE and 5 in PE/PVC). Ultra-Fast Liquid Chromatography with diode array detection (UFLC-DAD) was performed to quantify insulin (human and aspart) and preservatives (metacresol and phenol). Limited human insulin sorption was observed thirty minutes after the onset of infusion: 24.3 ± 12.9%, 3.1 ± 1.6% and 18.6 ± 10.0% for PVC, PE and PE/PVC respectively. With insulin aspart, sorption of about 5% was observed at the onset of infusion for all materials. However, there were interactions between phenol and especially metacresol with PVC, but no interactions with PE and PE/PVC. This study shows that insulin interacts with PVC, PE and PE/PVC at the onset of infusion. It also demonstrates that insulin preservatives interact with PVC, which may result in problems of insulin conservation and conformation. Some more studies are required to understand the clinical impact of the latter during infusion., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Plastic 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., Methods: The 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., Results: Significant 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., Conclusions: Clinicians 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.

Background: Infusion practices have been modified, especially for antineoplastic drugs, through the use of specific infusion devices with postadministration rinsing (PAR) so as to decrease occupational exposure to drugs. The aim of this study was to highlight how such infusion devices may impact the drug delivery of injectable drugs., Materials and Methods: Drug infusions were simulated with a radiotracer (99mTc) for 30 minutes to assess nine different infusion lines: 2 infusion methods without PAR (1 gravity-fed infusion and 1 pump infusion), 2 extension lines to be connected to standard infusion devices to allow PAR, and 5 specific infusion sets allowing a PAR. 99mTc was compounded in 250 or 100 mL of 0.9% NaCl solution. From the continuous recording of drug concentrations at device outlets, the areas under the drug concentration-time curve (AUC) were computed and divided in 2 parts: the AUCadm corresponding to the administration phase and the AUCrin corresponding to the rinsing phase. Their comparison to the initial activity led to compute the drug delivery. Results between groups were compared using a Kruskal-Wallis test (P < 0.05)., Results: Using standard infusion devices leads to administer only 91% and 88% when the drug is diluted in 250 and 100 mL, respectively. During the administration phase with the extension lines connected to infusion sets, between 90.8 ± 6.9% and 94.2 ± 1.8% of the drug is infused for 250 mL dilutions and 87.7 ± 2.0% for 100 mL dilutions. For specific infusion sets, the proportion of infused drug varied between 88.6 ± 6.0% and 95.3 ± 1.5% for dilutions in 250 mL and 71.2 ± 3.1% and 90.4 ± 2.8% for dilutions in 100 mL. Rinsing the lines means the remaining drug is administered a rinsing volume ranging between 47.0 ± 6.6 and 92.2 ± 8.9 mL according to the device and drug dilution., Conclusions: This study shows that drug delivery may differ according to infusion line and dilution volume. Further study is required to assess the impact of these devices on pharmacokinetics.

Background: International guidelines recommend noradrenaline (NA) as the vasopressor of choice to treat septic shock. The aim of this study was to determine the best way to infuse patients with NA., Methods: The in vitro study was designed to measure NA concentration at the end of each studied assembly line. Three infusion systems used the double pump method and three single pumps, which differed as regards NA concentrations (0,2 - 0,5 - 1 mg/h), dead space volume of the devices and the use of saline. Infusion systems were compared according to the time necessary to reach an NA mass flow rate steady-state plateau after the onset of infusion or after a flow change., Results: Times were significantly different between the six methods for infusing NA. The system using the double syringe method with a standard extension set was the longest to reach the steady state after the onset of infusion [40.00 min (19.57 - 49.22)]. The steady-state plateau was obtained most rapidly with the double-syringe pump systems using very low dead-space volume extension sets and single-syringe pump systems containing diluted noradrenaline at the beginning of NA infusion., Conclusion: A combination of a low dead-space volume extension set and a double pump method with a constant saline flow rate at 5 ml/h might be the solution to provide the most reliable NA infusion delivery., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective: Stopping and restarting carrier fluid flow and performing simultaneous drug infusions can lead to hazardous disturbances in drug delivery. The present study was designed to assess in vitro whether using a multi-lumen infusion access device could prevent noradrenaline disturbances., Study Design: In vitro laboratory work., Methods: Two infusion devices were studied: a standard device with a four-port manifold and a 150cm extension line and a nine-lumen infusion device (Edelvaiss-Multiline(®)) with eight accesses connected to nine separate lumens in a single tube of 150cm: seven accesses connected to seven peripheral lumens and one for the carrier fluid access connected to two lumens. Two experimental protocols of noradrenaline infusion were made: (a) drug flow rate change and (b) stop-and-go carrier fluid flows. Two parameters were studied: drug mass flow rate and flow change efficiency (FCE) calculated from the ratio of the area under the experimental mass flow rate curve to the area under the theoretical instantaneous mass flow rate curve., Results: Variations in noradrenaline mass flow rate were more rapid with the Edelvaiss-Multiline(®) when the noradrenaline infusion rate was increased or decreased. FCE was significantly different from one infusion device to the other during both noradrenaline flow rate increase (standard vs. nine-lumen: 58% vs. 84%; P=0.008) and decrease (175% vs. 108%; P=0.008). Decreased drug delivery after stopping carrier fluid flow (standard vs. nine-lumen: 21% vs. 98%; P=0.008) and sudden temporary increases on resumption (253% vs. 103%; P=0.008) were reduced in magnitude and duration when using the Edelvaiss-Multiline(®) with a significant difference in FCE between the two infusion devices., Conclusions: Using the nine-lumen infusion device reduces drug delivery disturbances during continuous intravenous infusion., (Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Background: The ability of an infusion set to deliver a specific amount of drug to the patient can be directly related to the presence of an antireflux valve and dead-space volume. In this study we quantified separately the impact of these 2 components on drug delivery., Methods: Various infusion sets were assessed differing in length, in dead-space volume, and with or without an antireflux valve. Noradrenaline was infused with a syringe pump simultaneously with a carrier flow. Effluent drug concentration was measured using ultraviolet spectrophotometry. Flow change efficiency (FCE) was calculated from the ratio of the area under the experimental mass flow rate curve to the area under the theoretical instantaneous mass flow rate curve., Results: The FCE for infusion sets with or without antireflux valves were significantly different 10 to 15 minutes after the start of an infusion at flow rates of 7 mL/h for noradrenaline and 35 mL/h to 70 mL/h for the carrier fluid. They were not different with a carrier flow of 115 mL/h., Discussion: These findings suggest that antireflux valves have a significant impact on FCE when the ratio of drug flow rate to carrier fluid flow rate is high. Infusion sets with very low dead-space volume connectors yield better FCE. There is a nonlinear relationship between dead-space volume and FCE 5 to 10 minutes after the onset of drug infusion., Conclusion: Care providers must consider dead-space volume and the presence of an antireflux valve when choosing their infusion sets.

Background: Multiaccess infusion sets allow multiple simultaneous infusions but may induce interference in drug delivery resulting from large variations in the delivery rate of potent drugs. In this study, we sought to understand the influence of multiaccess infusion device properties (dead space volume and antireflux valve [ARV]) on drug delivery during multi-infusion therapy., Methods: Infusion sets differing in length, dead space volume, and presence of an ARV were assessed. Three drugs were infused simultaneously through different access points, and their concentrations were obtained using UV spectrophotometric analysis of the effluent. Different infusion configurations were compared by assessing (1) the amount of drug delivered to the patient per unit of time, (2) the mean amount of drug delivered to the patient per unit of time during the steady-state infusion (mass flow rate plateau), and (3) flow change efficiency calculated from the ratio of the area under the experimental instant mass flow rate curve to the area corresponding to theoretical instant mass flow rate curve., Results: Infusion sets with lower dead space volumes offered significantly higher flow change efficiency (53.0% +/- 15.4% with a dead space volume equal to 0.046 mL 5 min after the start of infusion) than infusion sets with higher dead space volume (5.6% +/- 8.2% with a dead space volume equal to 6.16 mL), whatever the flow rate changes. Even in case of large dead space volumes, the presence of an ARV significantly increased the mass flow rate plateau (from 92.4% to 99.3% of the theoretical plateau without and with the presence of an ARV, respectively)., Conclusions: Multi-infusion therapy induces perturbation in drug delivery. These perturbations (lag time, backflow, and bolus) could be reduced by using infusion sets including very low dead space volume and an ARV.