The above is a link to a really good editorial on intraop methadone. I believe this a really underutilized opiate. Methadone is unique in that it is a NMDA receptor antagonist, and thus the only opiate that truly provides pre-emptive analgesia (although some data to support this for neuraxial opiates). In addition, methadone has a long half life and large therapeutic window. At doses greater or equal to 20 mg, the duration of methadone roughly equals its elimination time (22 hours). If one looks at figure 2, one can see that at doses less than 20 mg methadone is rapidly redistributed and behaves like any old narcotic. But above 20 mg, effect is determined by elimination half time and not redistribution. In addition, take note of the minimum effective analgesic concentration of 30 ng/ml while the toxic threshold (ie respiratory depression) is 100 ng/ml. The therapeutic window is large which greatly increases the safety margin of this drug. In the accompanying study, morphine consumption in the first 48 hours and pain scores in the first 48 hours were 50% LESS in the methadone group. Pretty amazing. Methadone is also extremely cheap. So why don't people use it? From personal experience, patients and heath care staff link methadone with heroine addiction. In addition, methadone does not offer a "buzz" or "high". Rather it provides analgesia and a clear head. However, many patients cannot separate the two. Also, many are concerned about giving a drug that last so long (even though the therapeutic window is so large). I treat it like Duramorph and make sure there are no stacking IV/PO/IM opiate orders or benzo orders for the first 24 hours. Also, the dose should be decreased in the elderly and debilitated, and it should be only used for painful surgery (open abdomen, spinal fusion etc.). I give 10 mg up front and titrate to resp rate at the end of the procedure (in the study they bolused 20 mg up front). Having used it several times, I am truly impressed with how alert, awake and pain-free these patients are (almost as if they had an epidural in place). At time when other traditional opiates are in short supply, perhaps everyone should re-evaluate the role of this cheap, safe and effective drug.