The Delivery of Drugs to Patients by Continuous Intravenous Infusion: Modeling Predicts Potential Dose Fluctuations Depending on Flow Rates and Infusion System Dead Volume

Abstract

IV drug infusion has the potential for dosing errors, which arise from complex interactions between carrier flows and the infusion set dead volume. We computed the steady-state mass of drug stored in the infusion set dead volume, using phenylephrine as a model compound. The mass of drug in the dead volume increases with stock drug concentration and desired dose but decreases with carrier flow rate. We also modeled the dynamic perturbations in drug delivery when a carrier is abruptly stopped. Rapid initial carrier flow rates lead to greater depression in drug delivery rate after carrier flow ceases. Rapid drug infusion rates lead to faster restoration of desired drug delivery. Finally, the time to reach a new steady-state after a change in drug delivery or carrier rate was computed. This time is longest for large stock-drug concentrations, larger dead volumes, and slower final carrier rates. These computations illustrate that (a) the dead volume may contain a large mass of drug available for inadvertent bolus, (b) cessation of carrier flow can profoundly reduce drug delivery, and (c) after a change in carrier flow or drug dosing, a significant lag is possible before drug delivery achieves steady state. Although computed for phenylephrine, the concepts are generic and valid for any drug administered by IV infusion.

Criteria for choosing an intravenous infusion line intended for multidrug infusion in anaesthesia and intensive care units

“…The impact of the dead volume on drug delivery depends on the total fluid flow rate which is the sum of the flow rate of the drug infusion and the flow rate of the carrier [71]. Mathematical models were developed to predict dynamic fluid perturbations and response time in drug delivery due to changes in carrier or pre-programmed flow rate [72]. The time to reach a new steady state after a change in drug delivery or carrier flow rate is longer for concentrated drug solutions, larger internal volumes and slower carrier flow rates.…”

Drug Flow Through Clinical Infusion Systems: How Modeling of the Common-volume Helps Explain Clinical Events

“…When all of the flows stop, the common-volume may function as a reservoir for a mass of forgotten drug. Even if medications and inert carriers are flowing, some mass of drug always resides within the common-volume (V) that can be estimated from the concentration in the reservoir (C res ), the drug (Q d ) and carrier (Q c ) flow rates [19]:…”

“…This drug mass can be accidentally delivered into patients if medications (e. g. antibiotics, muscle relaxants, opiates, anesthetics) are pushed upstream, carrier flows are suddenly increased, or another drug infusion is started at a high flow rate [19][20][21][22]. Indeed, this quantitative analysis could help predict the impact of provider inattention to the carrier flow rate as was illustrated in several of the clinical vignette's.…”

Relais des catécholamines en réanimation

“…En réanimation, les schémas de perfusion sont souvent complexes, parfois en contradiction totale avec des notions élémentaires de mécanique des fluides et d'hydraulique. En effet, la multiplication des points d'entrée dans un circuit [13], des longueurs et des compliances diffé-rentes de tubulures avec des volumes résiduels variables [14], ainsi que des « moteurs » de perfusion différents [15] (simple gravité ou seringue électrique), notamment en l'absence de valves antiretour [13] compromettent gravement l'objectif initial de l'administration d'un médicament à une dose et à un débit donnés au patient, et ce n'est pas parce que la seringue est montée sur une smart pump que le médica-ment sera effectivement délivré au patient. Ensuite, il n'est pas rare que l'injection d'un médicament ne modifie les régimes de perfusion des autres principes actifs administrés via le circuit complexe.…”