MeDD organized a 1-day symposium on infusion technology May 22. This symposium aimed at bringing together researchers, doctors, nurses and clinical physicist in the field of drug delivery. More than 80 people attended from 11 different countries. Below you will find the program and presentations.

Session 1 Results MeDD (1)

• Overview metrology for drug delivery (VSL, Peter Lucas)
• Clinical relevance of metrology for drug delivery (UMC Utrecht, Annemoon Timmerman)
• Calibration services for health care (METAS, Hugo Bissig)

Session 2 Multi-infusion and new technologies

• Towards a fully disposable pressure and flow sensor for industrial and medical applications (Imtek / University of Freiburg, Peter Koltay)
• Integration of a liquid flow meter for IV therapy (Sensirion, Daniel Längle)
• Towards system-Level modeling and characterization of components for intravenous therapy (Bronkhorst High-Tech / University of Twente, Joost Lötters)
• Drug-multiplexing (FH Lübeck, Bodo Nestler)

Session 3 Clinical applications and policy

• IV management and IV peripheral compliicatoins in a Neonatal Intensive Care Unit (UMC Utrecht, Agnes van den Hoogen)
• Precise and low variability drug dosing: where infusion technology and medication management meet (Utrecht University / UMC Utrecht, Toine Egberts)
• Infusion technology: challenges and pitfalls (Tergooi Hospital, Jeroen Verbunt)
• Improving insulin infusion method in the intensive care unit: from in vitro assessment to clinical data (Centre Hospitalier Régional / Lille University, Stéphanie Genay and Gilles Lebuffe)

Session 4 Results MeDD (2)

• Dosing errors in multi-infusion (UMC Utrecht, Roland Snijder)
• Assessment of several drug delivery devices (IPQ, Elsa Batista)
• Infusion best practices (UMC Utrecht, Annemoon Timmerman)

This best practice guide concerns various aspects related to infusion technology and is developed for clinical users such as nurses and physicians. This guide is put together based on a literature research and on lessons learned from MeDD and focuses on critical drug delivery applications. Here, critical is defined as those applications that require an accuracy of 95% or better. The technical aspects covered in this guide are therefore mostly related to how this accuracy can be ensured. Because the focus is at high accuracy applications, only syringe pumps are considered.

This E-learning is intended to create awareness on the risks of multi-infusion. Our aim is to improve your understanding of the physical characteristics of infusion systems. We discuss both pumps and disposables. We focus on their influence on the dose rate and potential dosing errors that can be clinically relevant.

In this report it is studied whether typical infusion pumps perform within accuracy specifications. Additionally, the startup time is studied. This is a very important parameter because it defines how long it takes before the patient receives the infusion doses that it needs. It will also be investigated how the compliance and start up delay depend on several physical parameters, drug delivery devices and accessories.

In task 1.4.2 the primary standards are subject to an inter comparison by means of a flow meter and a flow generator. This report covers the part of the characterization of the flow generator, in this case a syringe pump NEXUS 3000.

The aim of this report is to determine the influence of various physical parameters and operating conditions on the performance of various types of flow meters. These parameters have been selected that are most relevant for drug delivery applications: viscosity, temperature, back pressure and pulsatile flow.

An intercomparison has been organized with the purpose to determine the degree of equivalence of several newly developed primary standards for liquid flow rates from 3 mg/h up to 200 mg/h (equivalent with 50 nl/min to 3.3 μl/min). This intercomparison is complementary to EURAMET project 1291/ EURAMET.M.FF.S7 to cover even lower flow rates (project 1291 covers flow rates from 0.12 g/h up to 200 g/h, equivalent to 2 μl/min to 3.3 ml/min). This report discusses the protocol (measurement procedures) as well as the results following the intercomparison.

Medication protocols allow clinicians to administer the correct amount of medication to the patient. Medication protocols may include any procedure necessary to accomplish this goal safely, i.e. to prevent medical/medication errors.

In cooperation with the JRP partners, the UMC Utrecht has compiled and disseminated a survey about medication protocols amongst European hospitals. The aim was to acquire the most relevant medication protocols with an emphasis on preventing adverse drug events (ADE’s). Special attention has been given to multi-infusion and flow-rate variation. The analysis will be used to establish the necessary accuracy of the flow rate set point in order to be able to control the patient’s infusion treatment.

In this report the results of this survey are given and discussed.

The UMC Utrecht has developed an in-vitro measurement method to measure concentrations in infusion lines of multi-infusion while simulating several manual disturbances in one or more pumps. This method relies on spectrophotometry and flow meters. The spectrophotometry is used to determine the concentration of added dies whereas the flow meters measure the flow rate of the individual lines. The aim of this report is to provide a literature overview of studies describing similar multi-infusion concentration measurement and flowmetry methods.

Patients on the Intensive Care Unit almost always require infusion therapy. The continuous and stable infusion of drugs is necessary to stabilize and treat the patient. To predict the infused drug concentration, the UMC has developed a simulation model which is discussed in this technical report.

DTI and METAS have developed a flow meter performance tester for pulsating flow. The METAS setup covers a flow rate range of 1 ml/min to 1 ml/min with uncertainties ranging from 0.2% to 2.7%, depending on the flow rate and the fit window used. The DTI setup covers a flow rate range of 1 ml/min to 17 ml/min with uncertainties ranging from 0.03 % to 1.5 %, depending on the flow rate and the fit window used. These performance testers have been validated by means of an intercomaprison for a pulsatile flow generator. The validation showed consistency in the mean flow rates, the periodicity and the amplitudes of the pulsating flow. Click here to read the full report.

At the 2nd International Conference on Microfluidic Handling systems (MFHS 2014), MeDD presented various results. Click here for the proceedings of the volumetric-based primary standard of VSL. Click here for the proceedings of the gravimetric standard of METAS.

The aim of this work is to develop a physical model for the thermal processes that occur in the nano-flow generator of VSL, which is based on thermal expansion of water enclosed in a titanium reservoir. The model aims at establishing a numerical model for the flow rate in order to estimate the uncertainties involved. The numerical simulations are carried out with COMSOL. The complete report can be downloaded here.

In this work we develop a physical model which describes the behavior of an unsteady flow measured with a gravimetric set up. The model is based on equation for the physical shape of the interfaces between different fluids in the beaker (air-oil and oil-water) and on models of contact angles between these interfaces and the tube and beaker wall. In these models a dynamical contact angle is considered which can change with motion of the interfaces and which depends on velocity of the interfaces. The full report can be downloaded here.

M Ahrens, St Klein, B Nestler and C Damiani

This work focuses on the design and characterization of a system for measuring and calibration of liquid micro-flows down to 5 nL min⁻¹. The experimental setup relies on a telecentric imaging system mounted on a high-precision, computer controlled linear stage to track a moving liquid meniscus in a glass capillary. The position of the linear stage can be automatically adjusted to track the motion of the liquid front over distances of up to 15 cm. All fluidic components were placed inside a temperature regulated chamber at 36.0 ± 1.1 °C with a maximum variability ΔT = ± 0.1 °C for time intervals shorter than 1 h. The combined flow-rate uncertainty has been evaluated for measurement times from 15 s to 1 h and nominal flow rates between 5 and 50 nL min⁻¹. At 5 nL min⁻¹, an extended flow-rate uncertainty better that 8.3% can be attained for measurement times equal to or longer than 60 s. The uncertainty approaches asymptotically 5.4% for measurement times longer than 300 s or flow rates higher than 50 nL min⁻¹. The complete article is published in Measurement Science and Technology, 25, 015301, 2014 doi:10.1088/0957-0233/25/1/015301