Recent insights into the pharmacokinetics of spinal opioids and the relevance to opioid selection.

PURPOSE OF REVIEW: Spinal opioid administration was introduced into clinical practice nearly 25 years ago in the hope of producing intense spinal analgesia that was devoid of the dose-limiting side effects associated with systemic opioid administration. While spinal opioid administration can clearly be an effective analgesic technique, there is a widespread misconception that any opioid administered epidurally or intrathecally will produce analgesia by a selective spinal mechanism. This is simply not true; multiple opioids that are commonly administered spinally produce analgesia by uptake into the systemic circulation with subsequent redistribution to brainstem opioid receptors. In an effort to help clinicians understand why some opioids are not suitable for selective spinal analgesia, this review describes recent insights into the fate of intrathecally and epidurally administered opioids. RECENT
FINDINGS: A series of animal studies published over the last 4 or more years have provided the first measurements of opioid concentration in the epidural space, intrathecal space, spinal cord and peri-spinal tissues following intrathecal and epidural opioid administration. These studies characterize, for the first time, the factors governing the rate and extent to which different opioids redistribute from the epidural and intrathecal spaces to reach target opioid receptors in the spinal cord dorsal horn. The findings indicate that increasing lipid solubility decreases the spinal cord bioavailability of spinally administered opioids.
SUMMARY: These animal data help to explain multiple clinical studies that have demonstrated that the analgesic effect of spinally administered lipid-soluble opioids is due in part, if not exclusively, to uptake into plasma and distribution to brainstem opioid receptors.