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Exploring a case of incompatibility in a complex regimen containing Plasma-Lyte 148 in the pediatric intensive care
Niklas Nilsson1,2, Vivian Nguyen2, Katerina Nezvalova-Henriksen1,2
1Oslo Hospital Pharmacy, Rikshospitalet, Hospital Pharmacy Enterprise, Oslo, Norway.
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.
Insights
Midazolam and ketamine precipitate in intravenous solutions, posing a safety risk in pediatric intensive care. Fentanyl and potassium chloride are compatible with buffered electrolyte solutions.
Area of Science:
- Pharmaceutical Science
- Clinical Pharmacy
- Patient Safety
Background:
- Precipitation in intravenous lines during co-administration of multiple drugs is a critical safety concern in pediatric intensive care.
- A specific incident involved precipitation with a buffered electrolyte solution (Plasma-Lyte 148) and four co-administered drugs.
Observation:
- The study aimed to reproduce and investigate the precipitation risk of drug combinations with buffered electrolyte solutions and a glucose-containing variant.
- Physical compatibility was assessed using fentanyl, ketamine, midazolam, and potassium chloride in pediatric-relevant concentrations.
Findings:
- Midazolam and ketamine were found to cause visual and sub-visual particle formation when mixed with Plasma-Lyte 148, indicated by increased turbidity and Tyndall effect.
- Precipitation occurred due to exceeding solubility limits, as suggested by pH changes mirroring the buffered solution.
- Midazolam also precipitated with the lower-pH glucose-containing solution, while fentanyl and potassium chloride showed compatibility.
Implications:
- Midazolam and ketamine are incompatible with Plasma-Lyte 148 and should not be co-administered in the same intravenous line.
- Midazolam is also incompatible with the buffered electrolyte-glucose solution, necessitating careful drug selection and administration protocols.
- Fentanyl and potassium chloride are safe for co-administration with both tested electrolyte solutions.
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