The equianalgesic conversion ratio for IV to epidural to intrathecal opioids varies depending upon the meningeal permeability of the opioid in question. How lipophilic the drug is, as well as in part by its molecular weight, and possibly structure, affect meningeal permeability. The mechanisms of analgesia for intrathecal opioids result from a direct spinal mechanism, which occurs once the opioid has diffused into the intrathecal space, and a supraspinal effect, which occurs secondary to systemic absorption.
When administered epidurally, hydrophilic opioids work primarily through a direct spinal effect, as these drugs are less likely to be absorbed systemically in the epidural space, less likely to bind to epidural fat, and thus more likely move into the intrathecal space. They therefore have a greater meningeal permeability. Hydrophobic opioids work primarily via the supaspinal effect, as they are more quickly systemically absorbed when administered epidurally. For example, when administered as a prolonged infusion, hydrophobic epidural opioids such as fentanyl will reach plasma levels similar to IV infusions.
When administered directly into the intrathecal space, hydrophilic opioids are more likely to bind specific receptors in the dorsal horn, where they are most effective. The intrathecal concentration will remain elevated for longer periods of time as compared to lipophilic opioids, and thus are more likely to cause delayed respiratory depression via rostral spread. Hydrophobic opioids bind anywhere on the white matter of the spinal cord, and are more likely to leave the intrathecal space and be systemically absorbed. This causes less intrathecal spread of hydrophobic opioids, and thus a smaller area of analgesia, with lower risk of respiratory depression.
As a general rule of thumb:
- Morphine: 10mg IV = 1mg Epidural = 0.1mg Intrathecal (1/10 ratio; very hydrophilic)
- Hydromorphone: 1mg IV = 0.2mg Epidural = 0.04 Intrathecal (1/5 ratio; intermediate)
- Fentanyl: 100mcg IV = 33mcg Epidural = 6-10mcg Intrathecal (between 1/3 to 1/5 ratio; very lipophilic)