The impact of carrier flow rate and infusion set dead-volume on the dynamics of intravenous drug delivery

The dynamics of IV drug delivery resulting from drug infusions connected to main-line crystalloid carriers can be complex and depend on infusion set dead-volume, drug flow rate, and carrier flow rate. While the concept of dead-volume is intuitive, a lack of appreciation of the interaction with the carrier and drug flow rates can lead to unintended clinical effects resulting from large variations in the delivery rate of potent drugs. We derived mathematical models to quantify these interactions. Experimental simulation with methylene blue infusions tested these predictions. The models predict a lag in response time to changes in carrier or drug flow, which is proportional to the dead-volume and inversely related to the total flow rate. Increasing the carrier rate provides an acute drug bolus. Temporary reduction or cessation of carrier flow decreases the rate of drug delivery, potentially for prolonged periods. Furthermore, a drug bolus results from restoration of the carrier flow. The method of connecting an infusion to a carrier and the use history affects the dynamics of drug delivery. Thus, although complex, the impact of infusion set architecture and changes in carrier and drug flow rates are predictable. These quantitative studies may help optimize the safe use of IV drug infusion systems.