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We write to share important safety concerns about a local anesthetic being used primarily by surgeons with increasing frequency at our institution. Exparel® (Bupivacaine Liposome Injectable Suspension, Pacira Pharmaceuticals Inc., San Diego, CA) is a novel formulation of bupivacaine available in the United States since mid-2012. Bupivacaine is encapsulated within multivesicular liposomes and is released slowly, which is claimed to prolong its duration up to 72 hours. Its primary use is surgical wound infiltration.1Exparel is a white solution, similar to propofol (Fig. 1). Injection of a 20-mL vial (a total of 266 mg Exparel) could result in local anesthetic toxicity. The toxic dose on a milligram per kilogram basis is unknown because most of the drug is inactive because it is stored in liposomes. The manufacturer warns, however, that injection of Exparel must not occur within 20 minutes after the administration of nonbupivacaine local anesthetics such as lidocaine because it could cause the immediate release of bupivacaine from the liposomes.2Because the surgeon will be infiltrating Exparel and the anesthesiologist may concurrently be administering another local anesthetic, we risk a quickly deteriorating patient if a proactive approach to the safe use of Exparel is not taken. Discussing Exparel in the preincision timeout is advisable so its use is incorporated into the anesthetic plan. Furthermore, a “timeout” sticker on the vial would encourage communication between the surgeon and anesthesiologist, again before its use. Inservice education would benefit all members of the operating room team about the toxic potential of Exparel. Finally, stocking Exparel in the operating room satellite pharmacy and issuing a single vial at a time would prevent extra vials from being placed in or near the anesthesia drug cart so it is not mistaken for propofol, thus preventing drug substitution errors. Clearly, special safeguards are required for this unique drug with such high risk for catastrophe.Mark Burbridge, MDRichard A. Jaffe, MD, PhDDepartment of AnesthesiologyPerioperative and Pain MedicineStanford University School of MedicineStanford, Californiamarkburb@stanford.