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)

Assessment of stroke volumeindex with three different bioimpedance algorithms: lack of agreement compared to thermodilution

Objective: The accuracy of bioimpedance stroke volume index (SVI) is questionable as studies report inconsistent results. It remains unclear whether the algorithms alone are responsible for these findings. We analyzed the raw impedance data with three algorithms and compared bioimpedance SVI to transpulmonary thermodilution (SVITD). Design and setting: Prospective observational clinical study in a university hospital. Patients: Twenty adult patients scheduled for coronary artery bypass grafting (CABG). Interventions: SVITD and bioimpedance parameters were simultaneously obtained before surgery (t1), after bypass (t2), after sternal closure (t3), at the intensive care unit (t4), at normothermia (t5), after extubation (t6) and before discharge (t7). Bioimpedance data were analyzed off-line using cylinder (Kubicek: SVIK; Wang: SVIW) and truncated cone based algorithms (Sramek-Bernstein: SVISB). Measurements and results: Bias and precision between the SVITD and SVIK, SVISB, and SVIW was 1.0± 10.8, 9.8± 11.4, and -15.7± 8.2ml/m2 respectively, while the mean error was abundantly above 30%. Analysis of data per time moment resulted in a mean error above 30%, except for SVIW at t2 (28%). Conclusions: Estimation of SVI by cylinder or truncated cone based algorithms is not reliable for clinical decision making in patients undergoing CABG surgery. A more robust approach for estimating bioimpedance based SVI may exclude inconsistencies in the underlying algorithms in existing thoracic bioimpedance cardiography devices

Modeling friction, intrinsic curvature, and rotation of guide wires for simulation of minimally invasive vascular interventions

Obtaining the expertise to perform minimally invasive vascular interventions requires thorough training. In this paper, an algorithm for simulating minimally invasive vascular interventions for training purposes is presented and evaluated. The algorithm enables the simulation of completely straight guide wires as well as intrinsically curved ones based on applied translations and rotations. Friction between the guide wire and the vasculature is incorporated in the model. Quantitative validation is performed by comparing the simulated guide-wire position with the actual position as assessed by 3-D rotational X-ray imaging in physical experiments on a variety of vascular phantoms that truthfully represent human anatomy. The results show that for proper settings of the model's parameters, accurate simulations of guide-wire motion can be obtained, with an average precision of the guide-wire position of around 1.0 m

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

Impact of physical parameters on dosing errors due to a syringe exchange in multi-infusion therapy

Introduction Infusion therapy is challenging and dosing errors may occur due to physical phenomena related to the infusion hardware, despite the use of accurate syringe pumps. These errors typically occur after interventions, such as the exchange of a syringe. We aimed to characterize and quantify dosing errors due to a syringe exchange in relation to physical properties of infusion hardware. Methods An analytical simulation model was used to investigate dosing errors due to two different syringe exchange protocols (variations). Each protocol involved a fast syringe pump, containing a non-critical medication, and a slow syringe pump, containing a critical drug. The protocols were also reproduced in in vitro experiments to verify the simulation results. In addition, impact of syringe size, infusion set compliance, catheter diameter and the duration of the syringe exchange procedure on the quantity of the dosing errors was investigated. Results The syringe exchange of the slow pump resulted in an additional delay of up to 3536 seconds due to backflow. Syringe exchange of the fast pump resulted in an undiluted volume of critical drug (0.17 ml) accumulated in the infusion system, which may result in a dosing error rate of 2400 %. The quantity of the dosing errors are related to the syringe exchange duration; however, impact of infusion hardware properties is generally larger. Smaller syringes, catheters with larger diameters and less compliant infusion systems in general give rise to smaller dosing errors during a syringe exchange. If both lines are clamped, additional dosing errors can be prevented. Conclusion Infusion hardware has a substantial impact on the dosing errors during a syringe exchange. Clamping or blocking the infusion lines using, e. g. stopcocks, on all infusion lines during a syringe exchange is essential

Non-invasive measurement of volume-time curves in patients with mitral regurgitation and in healthy volunteers, using a new operator-independent screening tool

Left ventricular volume-time curves (VTCs) provide hemodynamic data, and may help clinical decision making. The generation of VTCs using echocardiography, however, is time-consuming and prone to inter-operator variability. In this study, we used a new non-invasive, operator-independent technique, the hemodynamic cardiac profiler (HCP), to generate VTCs. The HCP, which uses a low-intensity, patient-safe, high-frequency applied AC current, and 12 standard ECG electrodes attached on the thorax in a pre-defined pattern, was applied to five young healthy volunteers, five older healthy volunteers, and five patients with severe mitral regurgitation. From the VTCs generated by the HCP, the presence or absence of an isovolumetric contraction phase (ICP) was assessed, as well as the left ventricular ejection time (LVET), time of the pre-ejection period (tPEP), and ratio of the volumes of the early (E) and late (A) diastolic filling (E V/A V ratio), and compared to 2D transthoracic echocardiography (2D TTE) at rest. The reproducibility by two different operators showed good results (RMS = 5.2%). For intra-patient measurement RMS was 2.8%. Both LVET and the E V/A V ratio showed a strong significant correlation between HCP and 2D TTE derived parameters (p < 0.05). For tPEP, the correlation was still weak (p = 0.32). In all five patients with mitral regurgitation, the ICP was absent in the VTC from the HCP, whereas it was present in the 10 healthy volunteers, which is in accordance with pathophysiology. We conclude that the HCP seems to be a method for reproducible VTC generation, and may become a useful early screening tool for cardiac dysfunction in the future

Non-invasive measurement of volume-time curves in patients with mitral regurgitation and in healthy volunteers, using a new operator-independent screening tool

Left ventricular volume-time curves (VTCs) provide hemodynamic data, and may help clinical decision making. The generation of VTCs using echocardiography, however, is time-consuming and prone to inter-operator variability. In this study, we used a new non-invasive, operator-independent technique, the hemodynamic cardiac profiler (HCP), to generate VTCs. The HCP, which uses a low-intensity, patient-safe, high-frequency applied AC current, and 12 standard ECG electrodes attached on the thorax in a pre-defined pattern, was applied to five young healthy volunteers, five older healthy volunteers, and five patients with severe mitral regurgitation. From the VTCs generated by the HCP, the presence or absence of an isovolumetric contraction phase (ICP) was assessed, as well as the left ventricular ejection time (LVET), time of the pre-ejection period (tPEP), and ratio of the volumes of the early (E) and late (A) diastolic filling (E V/A V ratio), and compared to 2D transthoracic echocardiography (2D TTE) at rest. The reproducibility by two different operators showed good results (RMS = 5.2%). For intra-patient measurement RMS was 2.8%. Both LVET and the E V/A V ratio showed a strong significant correlation between HCP and 2D TTE derived parameters (p < 0.05). For tPEP, the correlation was still weak (p = 0.32). In all five patients with mitral regurgitation, the ICP was absent in the VTC from the HCP, whereas it was present in the 10 healthy volunteers, which is in accordance with pathophysiology. We conclude that the HCP seems to be a method for reproducible VTC generation, and may become a useful early screening tool for cardiac dysfunction in the future