title: The stability of a sulphite-free epidural analgesic solution containing fentanyl, bupivacaine, and adrenaline.
abstract: BACKGROUND
  Thoracic epidural infusion analgesia is optimised by using a triple component infusion containing a local anaesthetic, an opioid, and adrenaline. Adrenaline in solution is prone to oxidation, and stabilisers, such as antioxidants (e.g. sulphites) or chelators (edetates), are therefore commonly added. Sulphites may, however, have unwanted effects, especially allergic reactions. The aim of this study was to evaluate the stability of an analgesic infusion solution for epidural administration free of sulphites, containing adrenaline, fentanyl, bupivacaine, and disodium edetate.
  
  
  METHODS
  An epidural infusion solution containing adrenaline 2 μg/ml, fentanyl 2 μg/ml, bupivacaine 1 mg/ml, and disodium edetate 0.18 μg/ml was stored at 2-8°C for 4.5 months. A concentrate 11 times more potent, used for the production of the ready-to-use solution, was stored at 2-8°C for 9 months. Concentrations of the active ingredients were determined, pH was measured throughout the period, the clarity of the solutions was investigated, and the weight of the infusion bags recorded.
  
  
  RESULTS
  After 4.5 months at 2-8°C, the infusion solution contained adrenaline 97.5%, bupivacaine 100.9%, and fentanyl 102.6%. The pH stayed between 4.76 and 4.79, the solutions remained clear, and the weight was 99.9% of that found initially. The solution was also stable for 7 days at room temperature. The concentrate was stable (> 90%) for 9 months at 2-8°C.
  
  
  CONCLUSIONS
  The solution containing adrenaline, fentanyl, and bupivacaine, stabilised with disodium edetate, is stable for several months at 2-8°C, and at least for 7 days at room temperature without the addition of sulphites.
authors.affiliation: Hospital Pharmacy at Oslo University Hospital, Rikshospitalet, Sykehusapotekene HF, Oslo, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Brustugun
authors.forename: S
authors.initials: S
authors.lastname: Troland
authors.forename: H
authors.initials: H
authors.lastname: Breivik
mesh_terms: D015360:Analgesia, Epidural / Q000379:methods*; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002045:Bupivacaine / Q000008:administration & dosage*; D004355:Drug Stability; D004492:Edetic Acid / Q000494:pharmacology; D004837:Epinephrine / Q000008:administration & dosage*; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D012996:Solutions
chemical_list: D000779:Anesthetics, Local; D012996:Solutions; D004492:Edetic Acid; D005283:Fentanyl; D002045:Bupivacaine; D004837:Epinephrine