The delivery of drugs to patients by continuous intravenous infusion: modeling predicts potential dose fluctuations depending on flow rates and infusion system dead volume.

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.