Oslo Hospital Pharmacy, Rikshospitalet, Hospital Pharmacy Enterprise, Oslo, Norway.
Department of Pharmacy, University of Oslo, Oslo, Norway.
Paediatr Anaesth. 2023 Mar;33(3):211-218. doi: 10.1111/pan.14598. Epub 2022 Nov 21.
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.
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.
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.
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.
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.
在当地儿科重症监护病房，当四种药物与缓冲电解质溶液（百特公司的 Plasma-Lyte 148）一起使用时，观察到静脉导管中有沉淀。同时输注不相容的组合会带来安全隐患。
重现沉淀的临床病例。进一步探索和了解沉淀的风险，应研究不同成分的组合以及相应的电解质溶液与 5％葡萄糖（含 5％葡萄糖的 Plasma-Lyte 148）的组合。
测试了芬太尼、氯胺酮、咪达唑仑和氯化钾与缓冲电解质溶液的物理相容性。使用代表 10-40 公斤儿童的浓度和输注率来估计混合比例。进行了检测可见颗粒（丁达尔光束）和亚可见颗粒（光遮挡技术）的分析。将混合样品中的浊度和 pH 与未混合的对照进行了比较。
咪达唑仑和氯胺酮分别与 Plasma-Lyte 148 混合时均形成可见和亚可见颗粒。通过浊度增加和明显的丁达尔效应确认了颗粒的形成。混合样品的 pH 值与缓冲电解质的 pH 值一致，表明咪达唑仑的溶解度极限，以及在某些比例下氯胺酮的溶解度极限，已经超过。咪达唑仑与含糖产品混合时也会沉淀，该产品的 pH 值较低，更有利于保持咪达唑仑溶解。
重现病例表明，咪达唑仑和氯胺酮都促成了沉淀。咪达唑仑和氯胺酮均被评估为与缓冲电解质溶液不兼容，咪达唑仑也与缓冲电解质-葡萄糖溶液不兼容，不应在同一静脉导管中同时给药。芬太尼和氯化钾被解释为与两种缓冲电解质均相容。
