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Measurement of drug concentration and bacterial contamination after diluting morphine for intrathecal administration:
Aart Jan W Teunissen1, Mark V Koning2, Elisabeth J Ruijgrok3
1Anesthesiology, Maasstadziekenhuis, Maasstadweg 21, 3079DZ, Rotterdam, The Netherlands. teunissena@maasstadziekenhuis.nl.
Background:
Low concentrations of morphine are required for safe dosing for intrathecal injections. Sometimes, manual dilution of morphine is performed to achieve these low concentrations, but risks dilution errors and bacterial contamination. The primary goal was to compare the concentrations of morphine and bupivacaine between four groups of syringes. The secondary goal was to investigate the difference in contamination rate between these groups.
Methods:
Twenty-five experienced anesthesia providers were asked to prepare a mixture of bupivacaine 2.0 mg/ml and morphine 60 μg/ml using 3 different methods as clean and precise as possible. The fourth method used was the aspiration of ampoules prepared by the pharmacy. The concentrations of morphine and bupivacaine were measured by High-Pressure Liquid Chromatography (HPLC). The medication was cultured for bacterial contamination.
Results:
Group 1 (median 60 μg/ml; 95% CI: 59-110 μg/ml) yielded 3 outliers above 180 μg/ml morphine concentration. Group 2 (76 μg/ml; 95% CI: 72-80 μg/ml) and 3 (69 μg/ml; 95% CI: 66-71 μg/ml) were consistently higher than the target concentration of 60 μg. The group "pharmacy" was precise and accurate (59 μg/ml; 95% CI: 59-59 μg/ml). Group 2 and "pharmacy" had one contaminated sample with a spore-forming aerobic gram-positive rod.
Conclusion:
Manually diluted morphine is at risk for deviating concentrations, which could lead to increased side-effects. Medication produced by the hospital pharmacy was highly accurate. Furthermore, even when precautions are undertaken, contamination of the medication is a serious risk and appeared to be unrelated to the dilution process.
Insights
Manual dilution of morphine for intrathecal injections risks inaccurate concentrations and contamination. Pharmacy-prepared medication demonstrated accuracy, though contamination remains a concern regardless of the dilution method.
Area of Science:
- Anesthesiology
- Pharmacology
- Pharmaceutical Compounding
Background:
- Intrathecal injections require low morphine concentrations for safe administration.
- Manual dilution of morphine carries risks of dilution errors and bacterial contamination.
- Accurate morphine concentration is critical to prevent adverse effects.
Purpose of the Study:
- To compare morphine and bupivacaine concentrations across different syringe preparation methods.
- To evaluate bacterial contamination rates associated with various morphine dilution techniques.
Main Methods:
- Twenty-five anesthesia providers prepared morphine and bupivacaine mixtures using three distinct methods.
- A fourth group received pharmacy-prepared ampoules.
- Concentrations were analyzed via High-Pressure Liquid Chromatography (HPLC), and samples were cultured for contamination.
Main Results:
- Manual dilution methods (Groups 1-3) showed variable morphine concentrations, with some significantly exceeding the 60 μg/ml target.
- Pharmacy-prepared medication (Group 4) was precise and accurate (59 μg/ml).
- One contaminated sample occurred in Group 2 and the pharmacy group, identified as a spore-forming aerobic gram-positive rod.
Conclusions:
- Manual dilution of morphine for intrathecal use can lead to inaccurate concentrations and potential adverse events.
- Hospital pharmacy preparation ensures medication accuracy.
- Bacterial contamination is a risk irrespective of the dilution process, even with precautions.

