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TECHNOLOGY, COMPUTING, AND SIMULATION

Impact of Multiaccess Infusion Devices on In Vitro Drug Delivery During Multi-Infusion Therapy

Bertrand Décaudin, PhD^*, Sophie Dewulf, PharmD, Damien Lannoy, MSc^*, Nicolas Simon, MSc^*, Alexandre Secq, MSc, Christine Barthélémy, PhD^*, Bertrand Debaene, PhD, and Pascal Odou, PhD^*

From the *Department of Biopharmacy, Galenic and Hospital Pharmacy EA 4034—IFR114, Lille 2 University, Lille, France; Department of Pharmacy, Lille University Hospital, Lille, France; Department of Pharmacy, Dunkerque General Hospital, Dunkerque, France; and Anesthesia and Intensive Care Department, University Hospital, INSERM, Poitiers, France.

Address correspondence and reprint requests to Professeur Bertrand Debaene, Département d’Anesthésie-Réanimation, CHU de Poitiers, 2 rue de la Miletrie—BP 577, 86021 Poitiers Cedex, France. Address e-mail to b.debaene{at}chu-poitiers.fr.

BACKGROUND: Multiaccess infusion sets allow multiple simultaneous infusions but may induce interference in drug delivery resulting from large variations in the delivery rate of potent drugs. In this study, we sought to understand the influence of multiaccess infusion device properties (dead space volume and antireflux valve [ARV]) on drug delivery during multi-infusion therapy.

METHODS: Infusion sets differing in length, dead space volume, and presence of an ARV were assessed. Three drugs were infused simultaneously through different access points, and their concentrations were obtained using UV spectrophotometric analysis of the effluent. Different infusion configurations were compared by assessing (1) the amount of drug delivered to the patient per unit of time, (2) the mean amount of drug delivered to the patient per unit of time during the steady-state infusion (mass flow rate plateau), and (3) flow change efficiency calculated from the ratio of the area under the experimental instant mass flow rate curve to the area corresponding to theoretical instant mass flow rate curve.

RESULTS: Infusion sets with lower dead space volumes offered significantly higher flow change efficiency (53.0% ± 15.4% with a dead space volume equal to 0.046 mL 5 min after the start of infusion) than infusion sets with higher dead space volume (5.6% ± 8.2% with a dead space volume equal to 6.16 mL), whatever the flow rate changes. Even in case of large dead space volumes, the presence of an ARV significantly increased the mass flow rate plateau (from 92.4% to 99.3% of the theoretical plateau without and with the presence of an ARV, respectively).

CONCLUSIONS: Multi-infusion therapy induces perturbation in drug delivery. These perturbations (lag time, backflow, and bolus) could be reduced by using infusion sets including very low dead space volume and an ARV.