What Is the Optimal Carrier Fluid Rate for Reliable Hemodynamic Drug Infusion in Neonatal Patients?

Background: Critically ill neonates often require multiple hemodynamic medication infusions. At the necessary low flow rates of neonatal intensive care, equipment-related variations represent an important but hidden source of medication error. We previously observed that at low drug flow rates, backward upstream drug flow can occur at the junction with primary infusion, or “carrier,” fluid. Carrier flow also adds small variability in the total volume delivered. The constraints of low total fluid requirements in neonatal intensive care require optimizing carrier and drug flows, but published evidence is lacking.

Methods: We used our previously described drug infusion model, updated to our current hospital practice with a Bifuse connector. Diluted blue food dye was infused as drug from a 10-mL syringe via a smart syringe pump. Yellow dyed fluid was infused as carrier via a smart infusion pump. Drug concentrations (arbitrary units) were assessed every 5 minutes using two in-line spectrophotometers at the Bifuse carrier fluid tubing and distal T-connector. For all trials, drug flow was set at 0.2 mL/hr based on a standard epinephrine concentration of 40 mcg/mL and dose of 0.027 mcg/kg/min in a 5 kg infant. Carrier flows were tested at 1, 3, and 5 mL/h. Single-factor ANOVA and Levene’s test were performed using QI Macros 2019 software to compare steady-state drug delivery and variance.

Results: All trials reached steady-state flow by 30 minutes. Infusions were analyzed from 35 to 60 min. Drug concentration averages were 107, 141, 160 (arbitrary units) vs expected concentrations of 96, 256, and 416 for 1, 3, and 5 ml carrier rates, respectively. Drug delivery rates per hour were 13, 21, and 30 (units of fold dilution multiplied by volume infusion x 1,000) for 1, 3, and 5 mL carrier rates, respectively. Single factor ANOVA was p < .001 and Tukey’s honest significant difference was p < .001 for all pairwise comparisons. Variances of steady-state drug delivery were 4.5, 6.4, and 8.4 (Levene’s test p = 0.69) for 1, 3, and 5 mL carrier rates, respectively. No significant blue absorbance was detected in the Bifuse carrier tubing for any carrier infusion rate.

Conclusion: Higher carrier rates were related to higher drug concentrations and total drug delivery was proportional to carrier fluid rate in our low-flow drug model. Variances and thus, consistency, of drug delivery were similar. In contrast to our previous model, the use of a Bifuse prevented the backward flow of drug into the carrier line. When necessary, lower carrier rates may be safely used if drug dosage is empirically adjusted to effect. Lower carrier rates are important to consider because they can lower the total amount of fluid delivery to neonatal patients and overall cost.