Opioid conversion: IV and IT

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. Hydrophilic opioids are less likely to be absorbed systemically from the epidural space, less likely to bind to epidural fat, and thus reach higher concentrations in 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: 10 mg IV = 1 mg Epidural = 0.1 mg Intrathecal (1/10 ratio; very hydrophilic)
• Hydromorphone: 1 mg IV = 0.2 mg Epidural = 0.04 Intrathecal (1/5 ratio; intermediate)
• Fentanyl: 100 mcg IV = 33 mcg Epidural = 6-10 mcg Intrathecal (between 1/3 to 1/5 ratio; very lipophilic)

Updated definition 2020:

The appropriate conversion of intravenous opioids to equianalgesic epidural and/or intrathecal doses is not universally agreed upon at this time. There is little literature to support these conversions, with most recommendations being guided by expert opinion. Classically, it has been stated that morphine’s conversion from intravenous to epidural to intrathecal is 100 IV:10 EP:1 IT. However, many authors and practitioners would point out that this is potentially too conservative and would opt for using an IV:EP morphine ratio between 10:2 and 10:5. While the 100 IV:10 EP:1 IT ratio offers some guidance, it is further put into question when applied to opiates other than morphine that have different pharmacologic properties (i.e., lipophilicity and hydrophilicity). For instance, fentanyl is more lipophilic than morphine and hydromorphone. Therefore, using the most conservative ratio of 100 IV:10 EP:1 IT would potentially result in inadequate IT analgesia. Kim et al. conducted a retrospective study on the conversion of IT opioids in chronic pain patients with intrathecal delivery devices. They found that a safe and effective IV:IT fentanyl conversion ratio was between 32.7:1-20:1 and an IT morphine to IT fentanyl conversion ratio was closer to 15.7:1.