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In the field of oncology and in the setting of chronic pain, there are subsets of patients whose pain is refractory to usual drug dosages. Instead, to achieve acceptable pain control, combinations of local anesthetics and narcotics at elevated concentrations are required.
Although there is some literature on the compatibility of various combinations of these drugs, our institution needed data for these more concentrated solutions. To ensure patient safety and to ensure that acceptable expiry data were available, we performed physical compatibility testing for these more highly concentrated solutions.
We conducted a physical compatibility study of the various concentrations of bupivacaine used in the hospital with hydromorphone, morphine, or fentanyl, as listed in Table 1. The solutions were adjusted to volume with normal saline (Baxter Corporation, Mississauga, Ontario; lot W8F25B1, expiry September 2009) and were packaged in either polypropylene syringes (BD, Franklin Lakes, New Jersey; lot 8353527) or non-DEHP (di(2-ethylhexyl) phthalate) bags (Intravia, Baxter Healthcare Corporation, Deerfield, Illinois; lot UR09D07248), which were stored at 5°C for 28 days with protection from light. Samples (5 mL each) collected on the day of preparation (day 0) and on days 7, 14, 21, and 28 days after preparation were transferred into clear glass test tubes. The samples were inspected for the presence of precipitate and any change in colour, and the pH was measured with a calibrated pH meter (Accumet 25, Fisher Scientific Inc, Nepean, Ontario).
To achieve the higher concentrations of bupivacaine (i.e., 20.0 and 37.5 mg/mL), a 4% solution, compounded in our Pharmacy Department, was used. The 4% solution is used in the hospital’s Pain Clinic for patients whose pain cannot be managed at lower concentrations.
All solutions packaged in either polypropylene syringes or non-DHEP bags remained clear and colourless throughout the course of the study. The pH of the solutions changed only slightly during the study, with a general trend toward becoming more acidic (Table 1).
Previous studies1–7 investigated the chemical stability and/or physical compatibility of various concentrations of bupivacaine and one of the narcotics at lower concentrations in minibags and found them to be stable for at least 72 h at various temperatures. The chemical stability and/or physical compatibility of the lower concentrations of mixtures stored in syringes was also studied2,8–10; these mixtures were stable for at least 30 days at either room temperature or under refrigeration.
The compounded 4% solution of bupivacaine was needed to prepare the more concentrated solutions used in this study. Use of this solution might have caused a problem because the solution is at its saturation point for the drug at room temperature, and storage at 5°C might have caused precipitation. In this study, storage of solutions at 5°C represented a worst-case scenario. Barring future studies generating contrary information, mixtures stored at either 22°C or 37°C should also be considered physically compatible in either type of packaging (syringe or bag).
In conclusion, all solutions studied and packaged in either polypropylene syringes or non-DHEP bags were physically compatible for 28 days when stored at 5°C with protection from light.