Physiochemical Stability of Intravenous Fat Emulsion in Combination with Medications Used for Resuscitation

Abstract

Background: Intravenous fat emulsion 20% (IFE) is a potential therapy for lipophilic drug overdose. Data exists regarding IFE stability with medications in concentrations used for total parenteral nutrition [1]. However, IFE stability with drugs commonly used in resuscitation has not been assessed. This study's purpose is to examine the in vitro physiochemical stability of various combinations of IFE and medications commonly used in resuscitation by measuring the proportion of enlarged droplets greater than 5 micrometers (PFAT5) in IFE after mixture. Methods: We compared, in vitro, PFAT5 in various IFE-medication mixtures and a control. In order to assess the degree of coalescence, globule-size distribution was assessed according to method II of United States Pharmacopeia (USP) chapter 729 [2]. The volume weighted PFAT5 values were obtained with a Beckman-Coulter Multisizer 3 automated particle counter. IFE was mixed in a 1:1 ratio with standard concentrations of medications in Table 1. IFE-medication mixtures with PFAT5 > 0.05% at time 0 and 1 hour were considered coalesced per USP chapter 729. If any results of method II exceeded PFAT5 of the control, analysis of the globule-size distribution data was conducted using a one tailed Student's T test with a level of significance set at p < 0.05. Results: All samples tested including the normal saline control, exceeded the PFAT5 upper limit set forth by the USP chapter 729 (Table 1). Visual coalescence was observed with the glucagon sample at time 0 and 1 hour, and vasopressin at time 1 hour. (Table Presented) Conclusion: No IFE-medication mixture, including the saline control, met the USP chapter 729 PFAT5 standard. When compared to the control, standard concentrations and doses of calcium chloride, D50W, glucagon, insulin, lidocaine, magnesium sulfate, and sodium bicarbonate created a significantly higher PFAT5 immediately after mixing. IFE should be administered in a separate administration line when given with these medications.