This week we have a guest blog from Dr. Roland Snijder, Medical Physicist Resident at Haaglanden Medisch Centrum (NL). To obtain his PhD degree at the Utrecht University, Roland worked as a researcher on the multi-infusion project at the department of Medical Technology & Clinical Physics of University Medical Center Utrecht (UMC Utrecht). His research focused on investigating physical causes of dosing errors in multi-infusion systems. In this research flow characteristics of multi-infusion setups were investigated using Bronkhorst Coriolis flow meters. In this blog Roland explains more about his research.
What is infusion?
Most patients admitted to the hospital are treated with medication (pharmaceuticals). Especially in critical care, a substantial amount of patients require intravenous therapy. Intravenous therapy means that a solution of pharmaceuticals are administered directly into the veins. The process of administering pharmaceuticals directly into the veins is called infusion and is done using a vascular access device (e.g. a catheter), which is inserted into the vein.
The importance of an accurate flow
Often patients in critical care, most notably young and premature patients, suffer from conditions that require the intravenous administration of very potent and short acting pharmaceuticals. These pharmaceuticals typically require a very accurate administration where deviations in flow- and thus dosing-rate can easily result in dosing errors. For this reason, infusion or syringe pumps are used.
On top of this, vascular access to the patient is typically limited and therefore many infusion pumps have to co-administer through one catheter (multi-infusion), making the entire pharmaceutical delivery process complex and hard to predict.
Because dosing errors are common in clinical practice, it was clear that more research was required. Many of the results of this research can be found in the PhD-thesis: “Physical Causes of Dosing Errors in Patients Receiving Multi-Infusion Therapy”.
Fig 1. Example of a multi-infusion setup in clinical practice.
Flow measurement with Coriolis flow meter
We conducted a large amount of measurements to learn more about the flow characteristics of multi-infusion setups. These measurements were conducted using Bronkhorst Coriolis flow meters (series mini CORI-FLOW. These flow meters allowed us to measure the flow rate of infusion pumps very accurately, precisely and independent of the density of the solution being measured (although most of the solutions were similar to water).
The flow meters were also chosen because of the suitability for very low flow rates, infusion flow rates may be as low as 0.1 ml/h. Ultimately it is, of course, the dose rate or mass flow rate of the pharmaceutical administered to the patient that is important.
To measure this we used an absorption spectrophotometric setup, which enabled us to measure the concentration of a substance in a solution, i.e. a pharmaceutical or pharmaceutical-analogue. To convert density (e.g. µg/l) to a mass flow rate (e.g. µg/h), the cumulative flow rate (e.g. ml/h) of the infusion setup has to be measured as well.
First we used a precision balance for this but later in the research project we used the mini CORI-FLOW flow meter. The data from the precision balance was rather noisy, whereas the flow meter provided very clean data, which improved our measurements substantially.
However, one point of caution that has to considered is that flow meters do produce a pressure drop resulting in intrinsic flow resistance. The implications of this and how the measurement setup relates to a clinical situation is thoroughly explained in the PhD-thesis.
The research concluded that a wide variety of infusion components all had a particular, usually significant influence and, importantly, medical personnel is usually not aware of the implications this has for infusion therapy. Awareness of the underlying mechanisms of these effects through education and technical innovation were recommended. The Coriolis flow meters from Bronkhorst proved to be very suitable for gaining insight in the different mechanisms of infusion pump system failure.
Further reading: R.A. Snijder - Physical causes of dosing errors in patients receiving multi-infusion therapy (ISBN: 978-94-028-0382-2)
About the author:
Dr. R. A. (Roland) Snijder (1985) is Medical Physicist Resident at Haaglanden Medisch Centrum (NL). He obtained a master’s degree in Biomedical Engineering at the University of Groningen with a specialization curriculum in the area of medical physics (medical instrumentation and imaging). In his master thesis, conducted at the University Medical Center Groningen, he investigated the effects of using computed tomography (CT) for lung cancer screening. After finishing his master thesis in 2012, Roland went on to pursue a PhD degree at the department of Medical Technology and Clinical Physics of University Medical Center Utrecht (UMC Utrecht).
Dr. Roland Snijder (HMC)
Want to learn more about calibration of infusion pumps? Read the blog of Marcel Katerberg, explaining the calibration techniques to improve infusion pump performance.
A direct translation of the word ‘accreditation’ is providing trust. To measure this form of trust, standards are made to measure the expertise, impartiality and the level of continuous improvement of an organization. Laboratories that are accredited to the international standard ISO/IEC 17025:2005 have demonstrated that they are technically competent and able to produce precise and accurate test and/or calibration data.
Why are precise and accurate measurements important? For an example: If you pay the bill at the fuel station you trust that the amount you have to pay is an accurate equivalent of the amount of fuel which you filled-up. The same counts for many additional processes in which measurement equipment are used to secure the outcome of your process. An ISO/IEC 17025:2005 test certificate is the highest international level of calibration security which can be provided for measurement equipment. Bronkhorst is a proud owner of an accredited in-house ISO/IEC 17025:2005 Calibration Centre (BCC).
In this week’s blog I would like to take you with me to get a glance at our Bronkhorst Calibration Centre (BCC). This has been accredited since 2010 for gas, pressure and liquid flow calibration services.
For this, I followed Mandy Westhoff, one of our calibration centre operators, during her daily routines to get a realistic view on the activities of the calibration centre.
Why do flow meters have to be calibrated?
In general, all flow meters will be calibrated as a final step in production. The instrument with certain parameters will be compared with a fixed reference in certain environmental conditions, to provide real flow measurements.
Measuring equipment is used to secure the outcome of a process, process owners have to be able to rely on these measurements where high accuracy and – more and more – traceability play an important role, for example in the Pharmaceutical market. It is a way of risk management.
Throughout the years, we have noticed a distinctive increase in ISO/IEC17025:2005 calibrations in our calibration centre. An ISO/IEC 17025 calibration is often required as this is the highest level of calibration available in the market.
What kind of calibrations can be done in the calibration centre?
The Bronkhorst Calibration Centre is an independent department within the Bronkhorst organization and therefore not subjected to any commercial influences whatsoever.
It can be said that the tasks of the calibration centre are twofold:
- The BCC acts as an in-house lab which maintains all calibration standards used within the Bronkhorst organisation.
- The BCC acts as an external calibration lab which performs ISO/IEC 17025:2005 calibrations for anyone who wants this certification on their instruments, for both Bronkhorst instruments and other brands. Moreover, the BCC can perform adjustments on new and existing flow meters and controllers and calibration devices.
The Bronkhorst Calibration Centre, an external calibration lab
The scope of the calibration centre includes calibration of gas flow, liquid flow and pressure.
About 60-70% of the performed ISO/IEC 17025:2005 calibrations are ‘as found’ calibrations on used instruments. Many of our customers, especially in the Pharmaceutical market, Universities and Automotive industry, will send their instruments once a year for calibration. So they have a reliable instrument calibrated according to the highest level of calibration security which they can use as a reference for their own calibrations on-site.
To offer the highest standard of precise and accurate test and/or calibration data the environment of the laboratory is fully controlled. The calibration will be executed in a high-tech lab under conditioned circumstances by 21°C ± 2°C and a humidity of 50 ± 20%, which is outstanding. Even sunlight through the windows has been avoided and movement of people has been minimised as much as possible. Non-authorized personnel is not allowed to enter the calibration centre.
Can you explain the calibration process in the calibration centre?
After the acclimatisation process and setup, the operator will conduct a leakage test using the Flowbus Piston Prover (FPP). This test will be done prior to every calibration as a security check to maintain the high level of quality assurance.
After approval of the environmental conditions, the calibration starts. A standard calibration is performed on several measurement points. On these measuring points the accuracy of the instrument will be determined.
After a successful calibration the instrument is provided with a label mentioning the date of calibration and certificate number, so all can be traced back to the calibration dossier. The BCC coordinator will check if everything is done by protocol and all ISO/IEC 17025:2005 calibration dossiers will be sent to the BCC Officer to perform a final check.
How about training?
All our calibration operators are trained to perform gas, as well as pressure and liquid calibrations according to the ISO/IEC17025:2005 standard. Furthermore, we are taught how to maintain calibration devices, such as cleaning glass tubes and the chemicals which are used for calibration procedures.
Is it dangerous to do this type of work?
Training is the most important part. All our operators are highly competent and skilled employees. But still, all activities are primarily centered on human work. To keep the risk level as low as possible, everything is monitored closely during the calibration process and all materials used are checked on a regular base.
What makes your job interesting?
You never have a dull moment in this job, every day is different. The service you provide is always different, because it is customer specific. It is a nice idea that you can contribute to a successful customer’s process.
Working in flow, specifically low flow solutions, brings you into contact with applications and challenges that can be quite surprising. This week we discuss an opportunity for new calibration techniques to prove infusion pump performance.
Infusion pumps are well-known in medical applications. They come in multiple operating principles for pumping various fluids.
• Volumetric pumps are usually used for food and hydration at higher flow rates up to 1L/h.
• Syringe pumps are mostly used for accurately dosing low flow rates of down to 1ml/h or even lower.
We learned from users that the readout of a syringe pump shows the set point flow but it gives no feedback on the actual flow. Because of this lack of feedback on the actual flow being delivered, it is an area that should require regular accuracy checks. A regular programme of checks at a pre-determined flow rate or range is essential for ensuring that the delivery of fluid from the pump matches the expectations of the user. This is also an excellent opportunity to data log the performance of the pump for future reference and assists management purposes.
Moreover, we learned from medical engineering groups that there are currently two main calibrating techniques available for infusion pumps;
Volumetric measuring principle
The first uses volumetric measuring principles. This method usually needs a significant flow rate and minimum volume for achieving a reasonable accuracy within an acceptable period of time. This limits the ability to quickly check syringe pumps at the lowest flow rates and in critical applications. This creates a potentially inaccurate and time consuming calibration process.
Distance measuring principle
The second technique is to measure distance that the plunger travels over a pre-determined period of time and use that figure to extrapolate a figure for accept/reject. This technique is usually determined by the manufacturers of the instruments and carries with it a high degree of inaccuracy when adding together the manual method of measuring, the inaccuracy of the ruler, stopwatch and pump.
Improving response time and accuracy of infusion pump calibrations
Recognizing some of the flaws in the techniques above, and having talked to several professional working groups that use syringe pump calibration systems, we were excited to begin new research In these studies we test new sensor technology and techniques that could benefit the response time and accuracy of infusion pump calibrations.
To define the value of this study we identified together with the working groups potential applications in which accurate dosing is a critical process parameter. Below you will find the applications as identified:
• The use in pediatrics where patients are extra sensitive and vulnerable for wrong medicine dosage.
• Medication dosage at low rates where it is difficult to obtain a relative accurate and stable flow.
• Medication with a small therapeutic band in which a high accuracy is even more important.
• Multi infusion systems where multiple pumps are connected to a single cannula. In these systems the compliance of the used syringes and tubing can cause major errors in the actual dosage.
Low flow Coriolis sensor
We defined the hypothesis that the characteristics of a low flow Coriolis sensor could support the scope to improve the accuracy and response time of calibration systems used to calibrate syringe pumps. We demonstrated the validity of this hypothesis during an in-house study and at a hospital in the Netherlands. The Coriolis principle was chosen due to its proven accuracy and long term stability. Furthermore, due to their small internal volume and little pressure drop these instruments can be used in line to test complex multi infusion systems.
Surpassing the accuracy and response time
We bench marked the Coriolis sensor technique against an electronic analytical balance in house. The set-up of this experiment was approved by the Dutch Accreditation Council. Furthermore, we performed a bench mark study against an infusion calibration system at a hospital in the Netherlands.
The results of this study confirmed that the Coriolis sensor techniques can surpass the accuracy and response time of the incumbent measurement principles used in calibration systems.
Read about how Mandy Westhoff explains a typical day at Bronkhorst’s flow meter Calibration Centre (BCC)
Learn more about (mini) CORI-FLOW™ instruments combined with a valve or pump and watch the principle of operation of the mini CORI-FLOW Coriolis mass flow meter