Pump-driven clinical infusions: laboratory comparison of pump types, fluid composition and flow rates on model drug delivery applying a new quantitative tool, the pharmacokinetic coefficient of short-term variation (PK-CV)

Critically ill or anesthetized patients commonly receive pump-driven intravenous infusions of potent, fast-acting, short half-life medications for managing hemodynamics. Stepwise dosing, e.g. over 3-5 min, adjusts physiologic responses. Flow rates range from < 0.1 to > 30 ml/h, depending on pump type (large volume, syringe) and drug concentration. Most drugs are formulated in aqueous solutions. Hydrophobic drugs are formulated as lipid emulsions. Do the physical and chemical properties of emulsions impact delivery compared to aqueous solutions? Does stepwise dose titration by the pump correlate with predicted plasma concentrations? Precise, gravimetric, flow rate measurement compared delivery of a 20% lipid emulsion (LE) and 0.9% saline (NS) using different pump types and flow rates. We measured stepwise delivery and then computed predicted plasma concentrations following stepwise dose titration. We measured the pharmacokinetic coefficient of short-term variation, (PK-CV), to assess pump performance. LE and NS had similar mean flow rates in stepwise rate increments and decrements between 0.5 and 32 ml/h and continuous flows 0.5 and 5 ml/h. Pharmacokinetic computation predictions suggest delayed achievement of intended plasma levels following dose titrations. Syringe pumps exhibited smaller variations in PK-CV than large volume pumps. Pump-driven deliveries of lipid emulsion and aqueous solution behave similarly. At low flow rates we observed large flow rate variability differences between pump types showing they may not be interchangeable. PK-CV analysis provides a quantitative tool to assess infusion pump performance. Drug plasma concentrations may lag behind intent of pump dose titration.