The Impact of Carrier Flow Rate and Infusion Set Dead-Volume on the Dynamics of Intravenous Drug Delivery

Abstract

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.

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

“…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.…”

“…Benchtop (in vitro) modeling of initiating a drug infusion or changing the dose rate of an ongoing infusion shows that there can be a significant lag for the new concentration at the upstream side of the commonvolume to propagate to the patient and achieve the intended steady state delivery. This lag time can lead to delays in intended dose delivery that, under some conditions, can be surprisingly long [12,18,20,21,23]. For infusions into standard central venous catheters of sizeable dead-volume (9 Fr introducer sheath, dead volume~3.2 ml) with inert carrier flow rates designed to minimize excessive fluid administration (10 ml/hr), steady-state drug delivery rates may not be fully realized for over 20 min [18].…”

Improving noradrenaline infusion technique

“…We read with interest the recent letter regarding a drug error with Syntocinon â and the call for colour-coding for uterotonics [1]. Previous work suggests that a common cause of drug error is syringe swapping, which occurs most often between syringes of equal size, and is not eliminated by colour-coding of labels [2].…”

“…hypertensive peaks during the onset of infusion, depend primarily on infusion set characteristics [1][2][3][4]. Our aim was to determine in vitro whether a very low deadspace volume and anti-reflux valve infusion line assembly more accurately delivered a noradrenaline infusion compared with a standard double-pump assembly.…”

Preparing Drugs for Infusion Via Syringe Pump: A Key Step to Ensure Homogeneous Concentration

“…8 Material factors that have been identified as potential causes of drug-concentration discrepancies with syringe pumps include nonstandardized use of equipment such as tubes, valves, injectors, and syringes. [9][10][11] Documented human causes of inconsistent drug concentrations include drug mislabeling and improper manipulation of syringes. [12][13][14] Errors often found include confusion between 2 products and poor transcription of the prescription, all exacerbated by stress and fatigue.…”