Remifentanil Stability

To the Editor In a recent survey, 97.6% of responding anesthesia providers reported a shortage of ≥1 anesthetic drug.1 Drug shortages have increased >5-fold between 2005 and 2011.2 Nickerson and Chikumba3 point out that access to anesthetic medicines affects access to safe anesthetic care, in the United States and other high-income countries as well as in low- and middle-income countries. At the local level, the University of Utah Pharmacy and Anesthesia Departments have been working on ways to mitigate these shortages to minimize impact on patient care. One way to confront this shortage is to use high-concentration single-dose vials multiple times, which is allowable if the product is prepared within a sterile International Organization of Standardization 5 environment.4 An intravenous bolus of remifentanil provides profound but short-duration analgesia to facilitate brief, painful procedures, such as placement of retrobulbar blocks. The remifentanil package insert states that the reconstituted drug is stable for 24 hours at room temperature. From vials of remifentanil, the University of Utah Pharmacy prepares syringes of remifentanil 100 μg/mL for use by anesthesia providers. The unused syringes are disposed of daily. As a way to reduce demand on the pharmacist and reduce drug waste, thereby decreasing drug shortages, pharmacy personnel proposed evaluating the stability of reconstituted remifentanil when stored at room temperature, refrigerated, or frozen. Remifentanil (1 mg/mL lyophilized) was reconstituted with 0.9% sodium chloride to a concentration of 100 μg/mL in an International Organization of Standardization 5 environment. Aliquots were drawn into syringes and stored light protected at room temperature (22°C), refrigerated (4°C), or frozen (−18°C). Samples were analyzed by high-performance liquid chromatography on days 0, 1, 3, 9, 30, and 45. Inter- and intraassay precision and accuracy were adequately tested, with standard curves and quality control samples assayed on each testing day. Changes in drug concentration over time were mathematically computed for percentage change. Reconstituted remifentanil syringes stored at room temperature were stable for 45 days, with variation in drug concentration fluctuating from −1.5% to 3.5% over all testing days. The absolute concentrations were 99.8–104.9 μg/mL. Remifentanil syringes refrigerated displayed a drug concentration fluctuation from −0.2% to 4.9%, with absolute concentrations of 101.1–106.4 μg/mL. Remifentanil syringes stored frozen showed a drug concentration fluctuation of −0.8% to 2.9%, with absolute concentrations of 100.5–104.3 μg/mL (Table).Table.: Change in Drug Concentration Over Time as a Percentage of Day 0Regardless of storage condition, drug concentrations did not vary >5% for ≤45 days of storage. These data suggest that if prepared according to United States Pharmacopeia guidelines and stored refrigerated for short-term use or frozen for longer-term use, the drug concentration will remain within appropriate limits. This would decrease the usage cost for remifentanil, decrease demand on pharmacists for the daily preparation of syringes, and help alleviate shortage issues. Because of frequent drug shortages, it may be time to take a closer look at ways to prevent or combat these shortages, such as utilization of various storage methods. This also may translate into cost savings for the hospital and ultimately for the patient. Tatjana S. Bevans-Warren, PhD, CRNADepartment of AnesthesiologyUniversity of UtahSalt Lake City, Utah[email protected] Daniel O. Clegg Jr, PharmDDepartment of PharmacyUniversity of UtahSalt Lake City, Utah Derek J. Sakata, MDDepartment of AnesthesiologyUniversity of UtahSalt Lake City, Utah Christopher A. Reilly, PhDDepartment of Pharmacology/ToxicologyUniversity of UtahSalt Lake City, Utah