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

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.