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ARGUABLY, most clinicians who use opioids spinally believe that these drugs can spread rostrally in cerebrospinal fluid (CSF) to reach supraspinal sites. Therefore, many may be tempted to dismiss the work by Angst et al’ in this month’s ANESTHESIOLOGY as an unnecessary study with a predictable result. However, to do so would be inappropriate. The history of clinical medicine is embarrassingly full of “obvious truths’’ that were subsequently shown to be false when appropriately examined. Angst et al. ’ use a double-blind, randomized, crossover study design, coupled with segmental analgesia measurements for 24 h to investigate rostral spread of epidurally administered morphine. This powerful study design is a significant improvement over previous studies that sought to investigate rostral spread of spinally administered m~rphine .”~ As such, this study provides the strongest evidence to date that epidurally administered morphine does spread rostrally in CSF to reach brain stem levels. A further improvement over previous studies is the measurement of morphine plasma concentrations throughout the study period. The demonstration that morphine plasma concentrations bear no relation to the segmental analgesia produced by epidurally administered morphine is a clear indication of morphine’s spinal site of action. Demonstration of a spinal site of action is an underappreciated but essential component of any study investigating epidurally administered opioids. Demonstrating a spinal site of action is critical because any opioid placed in the epidural space in sufficient quantity will produce analgesia, if for no other reason than that the drug will eventually reach the plasma and

Rostral Spread of Epidural Morphine : The Expected and the Unexpected