Intravenous patient-controlled analgesia: in vitro stability profiles of mixtures containing fentanyl, hydromorphone, oxycodone, nefopam, ondansetron, and ramosetron

Background and objectives: Patient-controlled analgesia often involves combinations of multiple drugs. This study aimed to determine the stability of drug mixtures commonly used for intravenous patient-controlled analgesia. Materials and methods: We examined four of the most commonly used drug combinations in intravenous patient-controlled analgesia at our institution. Mixtures contained fentanyl (400 μg), either oxycodone (10 mg) or hydromorphone (4 mg), nefopam (20 mg), and either ondansetron (10 mg) or ramosetron (0.3 mg). Each drug mixture was diluted in 0.9% saline and stored in a portable patient-controlled analgesia system at room temperature (24 °C) for 96 h. Physical attributes including color, turbidity, and precipitation were assessed using digital imaging and optical microscopy. Sterility testing was conducted to assess for microbiological contamination. The pH of each mixture was monitored for up to 96 h after mixing. The concentration of each drug in the mixture was also evaluated using high-performance liquid chromatography. Results: All mixtures remained colorless and transparent with no visible sediment for 96 h. After 14 days of culture, none of the samples showed bacterial or fungal growth. The pH for all mixtures was maintained between 4.17 and 5.19, and the mean pH change in any mixture was less than 0.4 over the study period. The concentration of each drug remained between 90 and 110% of the initial value for 96 h after mixing. Conclusion: Four drug mixtures commonly used for intravenous patient-controlled analgesia are physiochemically stable and remain sterile for 96 h after mixing.