Analgesic medications are distributed to a variety of receptors within the central nervous system. Activity at these receptors (mu 1, mu, sigma, delta, kappa) results in both the beneficial pain-relieving effects of analgesics as well as undesirable side effects. The mixed agonist-antagonist class of analgesics offers the potential benefit of greater receptor site selectivity while diminishing the incidence of adverse sequelae, such as respiratory depression. Traditionally, it has been suggested that mixed agonist-antagonist medications may be associated with decreased analgesic effectiveness. However, newer agents of this mixed class may result in effective analgesia while diminishing the incidence of side effects.

Use of Dexmedetomidine to DiscontinueHigh-Dose Fentanyl TOTHE EDITOR: Dexmedetomidine is a central~-receptor agonist with sedative, analgesic, and sympatholytic properties.' Withdrawal fromopioid analgesics incites a hypernoradrenergic state. The ability of dexmedetomidine to modulate sympathetic outflow from the locus coeiuleus attenuatesthe physiologiceffects of opioid withdrawal and may allow for augmentation of inhibitory descending pain pathwaysP Wedescribe the use of dexmedetomidine to discontinue high-dose, postoperative fentanyl without sacrificing paincontrolin a patientchronically dependent on opioidanalgesics. Case Report. A 57-year-old man (106 kg) with medical history of cervical and lumbar radiculitis, diabetic neuropathy, postthoracotomy pain syndrome,and recurrentrenal calculi was admitted with bilateral distal femur fractures. Outpatientmedications for this patient's chronic pain syndromes included controlled-release (CR)oxycodone 320 mg every 8 hoursandhydromorphone 8 mg every6 hoursas needed for breakthrough pain, up to 32 mg daily. Followingbilateral total knee arthroplasty/openreduction internal fixation,the patientwas admittedto the intensivecare unit. On postoperativeday I, rapid sequence intubation was performed and the patient was sedated using midazolam. At this time, continuous fentanyl infusion was initiated at 25 Jlg/h (no bolus dose) and over the next 48 hours, titrated up to 500Jlg/h (Figure I). On postoperative day 5, the patient was successfully extubated. Despite