Bedside visualisation tool for prediction of deviation from intended dosage in multi-infusion therapy.

BACKGROUND: In multi-infusion therapy, multiple infusion pumps are connected to one single vascular access point. Interaction between pressure changes from different pumps may result in temporary dosing errors, which can be very harmful to the patient. It is known that these dosing errors occur. However, clinicians tend to find it hard to estimate the order of magnitude of these errors. METHODS: This research uses an existing mathematical model to create a bedside prediction tool that is able to provide clinicians with the dosing errors that will occur after flow rate changes in multi-infusion therapy. A panel of clinicians, consisting of both nurses and doctors, was formed, and, in order to assess the level of knowledge about dosing errors in multi-infusion, the panel was presented with four medication schedules in which a syringe exchange or change in flow rate took place. The panel was asked to predict the resulting dosing errors. RESULTS: A prediction tool was developed that describes a two pump multi-infusion system and predicts dosing errors resulting from changing the flow rate at one pump. 44% of the panel members wrongly predicted the impact of changing the set flow of liquid A on the flow of liquid B that reaches the patient. Nobody was able to correctly predict the dosing deviation if a very small catheter was used. After the prediction tool was shown, the clinicians indicated they had a improved understanding of what deviations to expect and that the tool would be useful in understanding multi-infusion dosing errors. CONCLUSIONS: Using the predictive tool to visualise the deviations from the set flow rate is an effective method to allow clinicians to gain insight in dosing errors in multi-infusion therapy. This knowledge can be used to better anticipate future dosing errors in clinical situations.

Effect of non-return valves on the time-of-arrival of new medication in a patient after syringe exchange in an infusion set-up.

The presence of a non-return valve in an infusion set-up is expected to affect the time-of-arrival of new medication in a patient after syringe exchange. Using Computational Fluid Dynamics (CFD) we have studied the flow through a typical non-return valve, focusing on two separate effects: (A) the overall delay in the time-of-arrival, and (B) timing effects due to the distortion of the Poiseuille flow profile in the non-return valve. The results show that (A) the additional delay in time-of-arrival of new medication, caused by the non-return valve alone, corresponds to the delay that would be caused by 11.2 cm of extra infusion line instead of the valve, and that (B) the non-Poiseuille flow profile inside the non-return valve gives rise to an extra slow wash-out of the last portion of the remnant fluid of the old medication. We conclude that awareness of these extra delays may be important for clinicians in certain time-critical situations.

Unexpected dosing errors due to air bubbles in infusion lines with and without air filters.

The effect of the presence of an air bubble, inside an infusion line, on the time (Tnew) needed for a new medication to reach the patient after a syringe exchange was studied in this paper. If an air bubble escapes through an air filter, then a sudden drop in pressure occurs, causing a relaxation of the compressible part of the syringe, followed by a gradual restoration of the flow rate in the line. We modeled this phenomenon mathematically and measured it experimentally in vitro. In an example with a pump flow rate of 5 mL/h and an air bubble of 1 cm length inside an infusion line (diameter 1 mm) with an air filter, both theory and experiment yield an additional increase of at least 600% in delay time if a naive estimate (based on the size of the bubble alone) is replaced by a more realistic estimate incorporating compressibility. Furthermore, we show that an air bubble in a line without air filter may increase Tnew by a factor 2, depending on the initial position of the air bubble. We conclude that an air bubble in an infusion line causes delays that may not be expected by health care professionals.

Metrology in health: challenges and solutions in infusion therapy and diagnostics.

The significance of Metrology in infusion therapy and diagnostics, both critical in health care safety and quality, is discussed in this article. Although infusion therapy is the most used form of drug administration, infusion errors are often made with reported dramatic effects in different applications, especially in neonatology. Adverse incidents, morbidity, and mortality have often been traced back to poor or inaccurate dosing. For critical infusion applications to vulnerable patients, well-controlled medication administration might be accomplished by improved dosing accuracy, traceable measurement of volume, flow, and pressure in existing drug delivery devices and in-line sensors operating at very low flow rates. To this end, the contribution of recently upgraded metrological infrastructures in European Metrology Institutes to a safer infusion therapy in health care is described in detail. Diagnostics, on the other hand is a sector characterized by rapid developments further triggered recently by the necessity for the management and prevention of infectious diseases like COVID-19. In this context, the impact of metrology in future large-scale commercialization of next generation diagnostics (e.g., point-of-care) is highlighted. Moreover, the latest contributions of Metrology in the development of traceable testing methods and protocols to ensure the sensitivity and accuracy of these devices are described.

Analytical method for calculation of deviations from intended dosages during multi-infusion.

BACKGROUND: In this paper, a new method is presented that combines mechanical compliance effects with Poiseuille flow and push-out effects ("dead volume") in one single mathematical framework for calculating dosing errors in multi-infusion set-ups. In contrast to existing numerical methods, our method produces explicit expressions that illustrate the mathematical dependencies of the dosing errors on hardware parameters and pump flow rate settings. METHODS: Our new approach uses the Z-transform to model the contents of the catheter, and after implementation in Mathematica (Wolfram), explicit expressions are produced automatically. Consistency of the resulting analytical expressions has been examined for limiting cases, and three types of in-vitro measurements have been performed to obtain a first experimental test of the validity of the theoretical results. RESULTS: The relative contribution of various factors affecting the dosing errors, such as the Poiseuille flow profile, resistance and internal volume of the catheter, mechanical compliance of the syringes and the various pump flow rate settings, can now be discerned clearly in the structure of the expressions generated by our method. The in-vitro experiments showed a standard deviation between theory and experiment of 14% for the delay time in the catheter, and of 13% for the time duration of the dosing error bolus. CONCLUSIONS: Our method provides insight and predictability in a large range of possible situations involving many variables and dependencies, which is potentially very useful for e.g. the development of a fast, bed-side tool ("calculator") that provides the clinician with a precise prediction of dosing errors and delay times interactively for many scenario's. The interactive nature of such a device has now been made feasible by the fact that, using our method, explicit expressions are available for these situations, as opposed to conventional time-consuming numerical simulations.

Hypertensive Crisis During Norepinephrine Syringe Exchange: A Case Report.

A 67-year critically ill patient suffered from a hypertensive crisis (200 mm Hg) because of a norepinephrine overdose. The overdose occurred when the clinician exchanged an almost-empty syringe and the syringe pump repeatedly reported an error. We hypothesized that an object between the plunger and the syringe driver may have caused the exertion of too much force on the syringe. Testing this hypothesis in vitro showed significant peak dosing errors (up to +572%) but moderate overdose (0.07 mL, +225%) if a clamp was used on the intravenous infusion line and a large overdose (0.8 mL, +2700%) if no clamp was used. Clamping and awareness are advised.

Dosing errors in preterm neonates due to flow rate variability in multi-infusion syringe pump setups: An in vitro spectrophotometry study.

BACKGROUND: Drug administration on the neonatal intensive care unit is often associated with adverse events. This may be due to dosing errors caused by multi-infusion setups. We aim to investigate these dosing errors. MATERIAL AND METHODS: N=3 experiment using a medication schedule, multi-infusion setup (three pumps) and disposables as applied on the NICU. In-line and real-time absorption spectrophotometry was used with dyes as substitutes for pharmaceuticals. Three flow rate changes lasting 1h were initiated. Subsequently, the possible dosing errors were estimated in the parallel pumps. In addition, startup durations, the times the flow rates required to reach steady state after significant dosing errors, as well as the total dosing error were measured. RESULTS: Contribution of the start-up delays to the cumulative dosing errors was the largest. However, initiated flow rate changes resulted in significant dosing errors in the parallel pumps as well. The total dosing error was not significant. The significant peak errors were between 48.2% and -32.5% at flow rate increase and decrease, respectively. Startup delays of up to 42.6min were measured. CONCLUSIONS: Applying multi-infusion while following a neonatal medication schedule may temporarily result in dosing errors, which can be relevant for fast-acting medications. Awareness may mitigate the risks.

Flow variability and its physical causes in infusion technology: a systematic review of in vitro measurement and modeling studies.

Infusion therapy is medically and technically challenging and frequently associated with medical errors. When administering pharmaceuticals by means of infusion, dosing errors can occur due to flow rate variability. These dosing errors may lead to adverse effects. We aimed to systematically review the available biomedical literature for in vitro measurement and modeling studies that investigated the physical causes of flow rate variability. Special focus was given to syringe pump setups, which are typically used if very accurate drug delivery is required. We aimed to extract from literature the component with the highest mechanical compliance in syringe pump setups. We included 53 studies, six of which were theoretical models, two articles were earlier reviews of infusion literature, and 45 were in vitro measurement studies. Mechanical compliance, flow resistance, and dead volume of infusion systems were stated as the most important and frequently identified physical causes of flow rate variability. The syringe was indicated as the most important source of mechanical compliance in syringe pump setups (9.0×10-9 to 2.1×10-8 l/Pa). Mechanical compliance caused longer flow rate start-up times (from several minutes up to approximately 70 min) and delayed occlusion alarm times (up to 117 min).

How to use current practice, risk analysis and standards to define hospital-wide policies on the safe use of infusion technology.

Infusion therapy is widely used in hospitals. It is well known that medication errors constitute one of the highest risks to patient safety, leading to numerous adverse events concerning incorrect application of infusion technology. Both clinical practice and in vitro studies show that infusion of multiple medications via one access point induces unwanted phenomena such as backflow and an incorrect system response to interventions. Within the Metrology for Drug Delivery project, we addressed the role of infusion devices in drug delivery. We surveyed current practices for application in hospitals to provide input to standards and quality norms for the materials used in infusion technology. Furthermore, we organized meetings with clinicians and other relevant stakeholders to set up a risk analysis-based infusion policy, accompanied by easy to access operating procedures on infusion technology. It was found difficult to establish clear-cut infusion safety guidelines based on quantitative data because of the many different application areas and stakeholders. However, both the expert team and the survey indicated the value of multidisciplinary qualitative discussion for defining best practices. We advise to incorporate specific requirements on infusion devices in protocols and standards, adjusted to specific applications, to ensure safe use of infusion technology.

How physical infusion system parameters cause clinically relevant dose deviations after setpoint changes.

Multi-infusion therapy, in which multiple pumps are connected to one access point, is frequently used in patient treatments. This practice is known to cause dosing errors following setpoint changes in the drug concentrations that actually enter the patients. Within the Metrology for Drug Delivery Project, we analyzed and quantified the two main physical phenomena leading to these errors: the "push-out" effect and the system mechanical compliance. We compared the dosing errors of a three-pump system with two infusion sets, both with and without anti-reflux valves, using in vitro spectrophotometric experiments. Additionally, computer simulations were used to study the compliance effect separately. We found a start-up time of more than 1 h, and a dosing error following a setpoint increase of another pump for the low flow rate pump, corresponding to 0.5 µg noradrenaline delivered in 8 min. We showed that the dead volume inside the tubes and syringe compliance produce opposite deviations from the setpoint values in the actual drug output concentrations, making the net result hard to predict and often counterintuitive. We conclude that metrology on compliance and push-out effects could be used by infusion device manufacturers to successfully improve drug delivery performance and relevant standards for high-risk multi-infusion applications.

Assessment of drug delivery devices.

For critical drug delivery, it is important to have a constant and well-known infusion rate delivered by the complete infusion set-up (pump, tubing, and accessories). Therefore, various drug delivery devices and accessories were tested in this article in terms of their infusion accuracy, start-up delay, response time, and dependency on the viscosity. These measurements were performed as part of the European funded research project MeDD. The obtained results show that the infusion accuracy of the devices is flow rate and accessory depended, especially for low flow rates. Viscosity does not have a significant impact on the flow rate accuracy.

No reduction of radiation dose following the introduction of dose-area product measurement in endoscopic retrograde cholangiopancreatography.

BACKGROUND: During radiological examinations such as endoscopic retrograde cholangiopancreatography (ERCP), it is recommended to record the dose-area product (DAP) to reduce the patient's and the physician's exposure to ionizing radiation. However, the effect of DAP measurement on the total radiation dose in ERCP procedures has never been assessed. OBJECTIVES: This study evaluated radiation dose use in ERCP procedures following the introduction of DAP measurement in the endoscopy unit. Also, patient-related, endoscopist-related and procedure-related factors associated with high DAP values were assessed. MATERIALS AND METHODS: All consecutive ERCPs from January 2008 to March 2011 were retrospectively reviewed. The DAP values and demographic-specific and disease-specific parameters were obtained from patient files and ERCP reports. RESULTS: A total of 279 ERCPs was analysed. The median DAP was 1907 cGy cm (range 316-7981). There was no significant decrease in the total radiation dose used in ERCPs following the installation of the DAP-meter in the endoscopy unit. Variables associated with significantly higher DAP values were precut papillotomy [odds ratio (OR) 2.44], hydrostatic balloon dilation (OR 3.56), stone extraction with a basket (OR 5.27) and procedures performed at the weekend (OR 6.43). CONCLUSION: The introduction of DAP measurement during ERCP did not result in a significant decrease in the total radiation dose. Several risk factors associated with a high radiation dose during ERCP procedures were identified, of which precut papillotomy and procedures performed during the weekend have not been described before in the literature. These factors enable endoscopists to more accurately identify patients at an increased risk of high radiation exposure.