FRCA Notes

Intrathecal Opioid Analgesia

This page is included on account of the 2019 SAQ on this topic (57% pass rate), in which a question on 'the mechanism of action of intrathecal opioids was answered poorly'.

Resources

  • Opioids administered intrathecally produce more potent and prolonged analgesic action than systemic opioids, but suffer from a number of issues

Commonly used

  • Morphine 75-300μg
  • Diamorphine 200-300μg
  • Fentanyl 12.5-50μg

Other opioids

  • Hydromorphone 5-10μg
  • Buprenorphine
  • Pethidine (meperidine)
  • Sufentanil
  • Tramadol
  • Pentazocine

Adjuncts

  • Clonidine (25-75μg) or Dexmedetomidine (5μg)
    • Prolong block and synergistic analgesic effect
    • Issues include significant hypotension, as well as bradycardia and sedation

  • Magnesium

Spinal cord

  • Primarily function by inhibiting nociceptive pathways in the spinal cord
  1. Reducing afferent signalling
    • Opioid is injected intrathecally
    • Binds to pre-synaptic G-protein coupled (Gi) opioid receptors in laminae I and II of the dorsal horn of the spinal cord i.e. the substantia gelatinosa
    • Within the neuron there is:
      • Inhibition of adenylyl cyclase, reducing cAMP levels
      • Increased K+ channel conductance
      • Reduced Ca2+ channel conductance
      • An overall hyperpolarisation of the cell membrane and reduction of neuronal cell excitability
    • There is reduced release of neurotransmitters from afferent nociceptive neurones
    • Overall reduced pain signal transmission

  2. Increasing activity at descending inhibitory pathways to the dorsal horn
    • Descending inhibitory pathways from the from the PAG via the nucleus raphe magnus modulate ascending (afferent) pain transmission
    • These pathways are themselves subject to inhibition by GABA-ergic interneurones
    • Opioids imapir GABA release from these interneurones
    • There is thus 'inhibition of the inhibitors' i.e. opioids cause activation of the inhibitory descending pathways
    • This further dampens ascending (afferent) nocicpetive neuronal transmission


Benefits of intrathecal opioids
Clinically significant opioid-sparing effect
Prolongs duration of spinal analgesia
Improved pain at rest at 24hrs
Improved dynamic pain at 48hrs
Overall reduced pain scores for up to 72hrs
Marginally reduced hospital length of stay
High patient satisfaction
Suitable in patients where coagulopathy precludes catheter-based techniques
Incidence of some side-effects is not different to systemic opioids


  • Finite duration of effect
  • May be less effective than epidural analgesia for some patient groups

  • Increased risk of common opioid-induced side-effects: PONV, urinary retention, hypotension

Pruritus

  • Dose-dependent, significantly higher rates of pruritis than for systemic opioids:
    • 30-40% for morphine overall, but 60-100% in the obstetric population
    • 27% for IT fentanyl

  • Mechanisms
    • Stimulation of spinal and supraspinal mu-opioid receptors, including the trigeminal nucleus causing facial itch
    • Dose-dependent increases in plasma serotonin levels (approx. 550% following 250μg intrathecal morphine)

  • Management
    • Ondansetron 4-8mg is effective for treating established pruritus and has a preventative effect in non-obstetric populations
    • Naloxone or other partial opioid antagonists such as nalbuphine or pentazocine
    • Mirtazepine
    • Droperidol

Respiratory depression a.k.a opioid-induced ventilatory impairment (OIVI)

  • There are issues in assessing and comparing this side-effect due to:
    • Large sample size requirements for such an infrequent event
    • Inconsistent definitions, variably using respiratory rate, desaturation or need for supplemental oxygen, or need for opioid antagonists

  • The timing of respiratory depression with morphine is delayed, with peak effects at 4-8hrs and altered ventilatory response to CO2 up to 20hrs

  • In overall summary:
    • IT morphine is more likely to cause respiratory depression than IT fentanyl
    • The risk of respiratory depression with morphine will depend on definition used, opioid used, patient cohort and surgery performed but generally ranges from 1-9%
    • Respiratory depression is more likely at higher (>300μg) morphine doses
    • The rate of respiratory depression with low dose IT morphine may be (near-) equivalent to that of systemic opioids
    • The lowest effective dose of IT morphine should be used in order to reduce the risk of delayed respiratory depression
    • Patients who've received IT opioids should have monitoring for OIVI for 18-24hrs post-operatively