Stability of an epidural analgesic admixture of levobupivacaine, fentanyl and epinephrine

Helin-Tanninen, Minna; Lehtonen, Marko; Naaranlahti, Toivo; Venäläinen, Taisa; Pentikäinen, Jaana; Laatikainen, A.; Kokki, Hannu

doi:10.1111/jcpt.12035

Cited by 7 publications

(6 citation statements)

References 15 publications

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“…Helin-Tanninen et al reported that when drug mixtures are stored at room temperature without a rigid secondary package, evaporation of the solution through the polyester infusion bag significantly increases the drug concentrations (49). In the present study, there was no consistent change in the concentra-tion of drugs over time, except for the concentration of ketorolac in mixtures 3 and 4.…”

Section: E835contrasting

confidence: 60%

Microbiological and Physicochemical Stability of Fentanyl, Oxycodone, Hydromorphone, Ketorolac, Ramosetron, and Ondansetron for Intravenous Patient-controlled Analgesia: An In Vitro Study

et al. 2021

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BACKGROUND: Postoperative patient-controlled analgesia provides pain relief, encourages early mobilization, and results in a shortened hospital stay. Patient-controlled analgesia involves the mixing of different types of drugs. When using patient-controlled analgesia, it is important to confirm the microbiological and physicochemical stability of each drug in a mixture to guarantee that the drug is delivered to the patient in an unaltered form. OBJECTIVES: To confirm the microbiological and physicochemical stability of various drug mixtures for intravenous patient-controlled analgesia. STUDY DESIGN: An in vitro protocol to examine the microbiological and physicochemical stability of the most commonly used postoperative intravenous patient-controlled analgesia mixtures at our institution. SETTING: In vitro laboratory study. METHODS: Each mixture contained a total of 4 drugs: fentanyl 400 µg, ketorolac 30 mg, either hydromorphone 4 mg or oxycodone 10 mg, and either ramosetron 0.3 mg or ondansetron 10 mg. Each mixture was placed in a portable patient-controlled analgesia system containing 0.9% saline and stored at a constant temperature of 24°C for 96 hours. Physical properties (color, transparency, and sedimentation) were observed with the naked eye and optical microscopy. Sterility testing was performed to assess microbiological contamination in the drug mixture during the 96-hour study period. The pH of each mixture was evaluated for up to 96 hours after mixing. The concentration of each drug was evaluated by high-performance liquid chromatography every 24 hours until 96 hours after mixing. RESULTS: All mixtures appeared visibly transparent, and no sediments were visible under the microscope. Bacterial or fungal growth was not observed in any of the samples after 14 days of incubation. The pH variations in all mixtures were maintained within 0.25 over the 96-hour study period. The concentration of drugs, except ketorolac, ranged from 90–110% of the initial concentration up to 96 hours after mixing. In the mixtures with a pH of 4.21–4.39, the concentration of ketorolac significantly decreased at 24 hours and 48 hours. LIMITATIONS: Confirmation of the stability of drugs in vitro does not automatically ensure that the pharmacokinetics and pharmacodynamics of the drugs are not altered in vivo. CONCLUSION: With the exception of ketorolac, the drugs used in the intravenous patient-controlled analgesia drug mixtures in this study were physicochemically stable up to 96 hours after mixing. The concentration of ketorolac decreased in more acidic mixtures. KEY WORDS: Patient-controlled analgesia, multimodal analgesia, stability, fentanyl, oxycodone, hydromorphone, ketorolac, ondansetron, ramosetron

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Section: E835contrasting

confidence: 60%

Microbiological and Physicochemical Stability of Fentanyl, Oxycodone, Hydromorphone, Ketorolac, Ramosetron, and Ondansetron for Intravenous Patient-controlled Analgesia: An In Vitro Study

et al. 2021

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“…We, therefore, evaluated the physical, chemical, and microbiological stabilities of mixtures containing fentanyl, either oxycodone or hydromorphone, nefopam, and either ondansetron or ramosetron. Helin-Tanninen et al (2013) reported that a significant increase in drug concentration can occur as a result of evaporation through polyester injection bags when drug mixtures are stored at room temperature in the absence of tightly closed secondary packaging. In our study, there was no significant increase or decrease in the concentration of each drug in any of the mixtures up to 96 h after mixing, suggesting that evaporation did not occur from the portable balloon infusion pump used in this study.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…The stability of that solution was documented for 184 days at both 4°C and 22°C . In another study, a solution containing levobupivacaine (570 μg/ml), fentanyl (3.7 μg/ml), and adrenaline (1.9 μg/ml) was shown to be stable for 60 days at 6°C and 40 days at 22°C . The adrenaline solution for injection used for preparing this solution (Adrenalin 0.1 mg/ml, Leiras, Helsinki, Finland) contained edetate and 1 mg/ml sodium metabisulphite.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, it was stated that the degradation of adrenaline in a triple component analgesic admixture containing levobupivacaine, fentanyl, and adrenaline was mostly dependant on light – light having a destabilising effect . However, the adrenaline injection used for the preparation of that solution (Adrenalin 0.1 mg/ml, Leiras) contains sulphite, and this may have influenced the result.…”

Section: Discussionmentioning

confidence: 99%

The stability of a sulphite-free epidural analgesic solution containing fentanyl, bupivacaine, and adrenaline

Brustugun

Troland

Breivik

2013

Acta Anaesthesiol Scand

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Stability of an epidural analgesic admixture of levobupivacaine, fentanyl and epinephrine

Abstract: Epidural analgesic admixtures of levobupivacaine and fentanyl with or without epinephrine have to be stored in a tightly closed secondary package protected from light. The extended stability, up to 60 days, in a refrigerator enables the centralized preparation in the hospital pharmacy.

Cited by 7 publications

References 15 publications

Microbiological and Physicochemical Stability of Fentanyl, Oxycodone, Hydromorphone, Ketorolac, Ramosetron, and Ondansetron for Intravenous Patient-controlled Analgesia: An In Vitro Study

Microbiological and Physicochemical Stability of Fentanyl, Oxycodone, Hydromorphone, Ketorolac, Ramosetron, and Ondansetron for Intravenous Patient-controlled Analgesia: An In Vitro Study

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

The stability of a sulphite-free epidural analgesic solution containing fentanyl, bupivacaine, and adrenaline

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