Exploring a case of incompatibility in a complex regimen containing Plasma‐Lyte 148 in the pediatric intensive care

Abstract

Background: In the local pediatric intensive care unit, precipitation was observed in the intravenous catheter upon co-administration of four drugs together with the buffered electrolyte solution (Plasma-Lyte 148, Baxter). Co-infusion of incompatible combinations represents a safety concern. Aims:To reproduce the clinical case of precipitation. To further explore and understand the risk of precipitation, different combinations of the components as well as the corresponding electrolyte solution with 5% glucose (Plasma-Lyte 148 with 5% glucose) should be investigated. Methods: Physical compatibility of fentanyl, ketamine, midazolam, and potassium chloride was tested in combination with the buffered electrolyte solutions. The concentrations and infusion rates representative of children 10-40 kg were used to estimate mixing ratios. Analyses detecting visual particles (Tyndall beam) and sub-visual particles (light obscuration technology) were undertaken. Measured turbidity and pH in mixed samples were compared with unmixed controls.Results: Both midazolam and ketamine showed formation of visual and sub-visual particles upon mixing with Plasma-Lyte 148, respectively. Particle formation was confirmed by increased turbidity and a distinct Tyndall effect. pH in mixed samples mirrored the pH of the buffered electrolyte, suggesting that the solubility limits of midazolam, and in some ratios also ketamine, were exceeded. Midazolam also precipitated in combination with the glucose-containing product that held a lower pH, more favorable for keeping midazolam dissolved.Conclusions: Replication of the case revealed that both midazolam and ketamine contributed to the precipitation. Midazolam and ketamine were both evaluated as incompatible with the buffered electrolyte solution and midazolam also with the buffered electrolyte-glucose solution and should not be co-administered in the same i.v.catheter line. Fentanyl and potassium chloride were interpreted as compatible with both buffered electrolytes.

Co-administration of Intravenous Drugs: Rapidly Troubleshooting the Solid Form Composition of a Precipitate in a Multi-drug Mixture Using On-Site Raman Spectroscopy

“…Developing validated methods for multiple component solutions demands time and resources, and relying on visual control for detection of precipitates does not cover sub-visible particles neither does it provide the solid form identity of the precipitate. The current methods for assessment of physical y-site compatibility include pH and turbidity measurements, sub-visual particle counting, osmolality, and if one of the components are or contain a parenteral lipid emulsion also mean droplet diameter measurement, and estimation of percentage of large diameter droplets (>5 μm, PFAT5). − However, in neither of these methods, the identity of the precipitate can be determined beyond theoretical predictions based on solubility and pH. Raman spectroscopy could potentially redeem some of the challenges met with classical compatibility testing, ,, extending the limits of what can be achieved.…”