Physical causes of dosing errors in patients receiving multi-infusion therapy

Most patients in critical care receive intravenous infusion therapy, which is challenging for several reasons. Firstly, critically ill patients often require the support of drugs that must be administered continuously, accurately and precisely. Syringe pumps are typically used for this purpose. Secondly, the challenging nature of vascular access, its associated risk of catheter-related infections and sepsis, and drug incompatibility, require that multiple drugs are co-administered through one multiple-in single-out infusion set and one catheter lumen. This technique of co-administering drugs is known as multi-infusion and has been associated with dosing errors caused by physical effects related to the infusion hardware, despite the use of accurate syringe pumps. A final complicating factor is that many patients, especially neonates, cannot tolerate large quantities of fluids. For this reason, the flow rate has to be low, which requires the drug solution to be relatively concentrated in order to be able to administer the effective dose. From this it follows that small fluctuations in flow rate can lead to substantial dosing errors. The general objective of this thesis was to investigate physical causes of dosing errors - related to infusion hardware - in patients receiving multi-infusion therapy, and the clinical consequences of these dosing errors. In clinical practice, the dosing errors are typically followed after interventions such as flow rate changes, starting of the infusion pump from standstill, syringe exchanges and vertical displacement of the pump relative to the patient. The errors may occur in the pump in which the interventions were conducted as well as the other parallel pumps that co-administer medication on a common infusion set and catheter to the patient. The most important physical effects that cause dosing errors in patients receiving multi-infusion therapy are mechanical compliance, flow resistance and dead volume. The dosing errors caused by the interplay of all these effects can be counter-intuitive and ambiguous. Nevertheless, in this thesis it was shown that the dosing errors can be predicted, both by modeling and in vitro measurements. Dosing errors due to physical causes related to infusion hardware and interventions have the potential to have measurable, clinically relevant impact in patients. Technical innovations, standards, regulations and creating awareness through education programs may mitigate the dosing errors and the clinical consequences thereof. The results of this research may therefore contribute to patient safety.