Neuraxial opioids: tolerance


The four common side effects/complications include respiratory depression, urinary retention, nausea/vomiting, and pruritus, the most serious being a dose-dependent, delayed respiratory depression. Early respiratory depression occurs within 2 hours and is likely due to systemic absorption. Delayed respiratory depression can occur between 6-24 hours after administration. It results from cephalad migration to the ventral medulla. Estimated incidence is 0.01-7% with single injection intrathecal morphine and 0.08-3% with single injection epidural morphine, depending on the definition of respiratory depression that’s used. The incidence is higher following intrathecal vs. epidural opioids. Most cases occur in those who are also receiving other opioids/sedatives. The elderly and those with sleep apnea are more vulnerable.

Pruritus is very common, most cases being mild, but about 1% have severe itching. It is not due to histamine release but likely from cephalad migration in the CSF and interaction with opioid receptors in the trigeminal nucleus. Thus, antihistamines are likely not beneficial, and mixed agonist-antagonists should be considered.

Intrathecal opioids are often used to treat chronic pain, especially cancer pain. One of the drawbacks of this therapy is the development of tolerance – the need to increase dose requirements-over time to maintain pain relief.


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