FRCA Notes

Adjuncts to Local Anaesthetic for Regional Anaesthesia

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  • Peripheral nerve blocks using local anaesthetic are more effective than opioids alone for post-operative analgesia, yet are beset by a limited duration of analgesic action
  • The duration can be improved by use of an indwelling catheter and continuous infusion of LA, but this comes with its own risks and hurdles:
    • Catheter-associated issues such as migration, nerve irritation, leakage or inflammation
    • Infection
    • Pump-related issues
    • Increased healthcare costs
    • Higher risk of LA toxicity
  • The co-administration of adjuncts alongside local anaesthetic, either IV or perineurally, can increase the duration of action of analgesia from peripheral nerve blocks without these catheter-associated risks
  • Localised vasoconstriction via ɑ1 effect reduces LA uptake
  • Dose 2.5 - 5μg/ml

  • Benefits:
    • Increases during of analgesia by approximately 1hr
    • Reduced risk of LA toxicity
    • Helps detect intravascular injection of LA (although of dubious sensitivity)

  • Downsides:
    • Does not increase the duration of longer-acting agents e.g. ropivacaine, bupivacaine
    • May cause local neurotoxicity via vasoconstriction and ischaemia
    • Systemic effects e.g. hypertension and tachycardia may cause issues, especially in those with pre-existing myocardial disease

  • Bind to activated nucleotide-gated channels responsible for restoring resting membrane potential
  • This causes hyperpolarisation of Aδ & C-fibres and prevents further action potential generation
  • Clonidine may also cause a degree of local vasoconstriction via its ɑ1 effect

Clonidine

  • Partial ɑ2-adrenoreceptor agonist
  • Dose 150μg (30 - 300μg)

  • Benefits:
    • Prolongs duration of analgesia by up to 2hrs
    • Effect more prominent with shorter-acting (prilocaine, lidocaine) than longer-acting (bupivacaine, ropivacaine) agents
    • Not associated with neurotoxicity

  • Downsides:
    • Tends to prolong motor block too
    • Cardiovascular side-effects, particularly hypotension, bradycardia, sedation or fainting

Dexmedetomidine

  • Selective ɑ2-adrenoreceptor agonist
  • Dose 50-60μg

  • Benefits:
    • Prolongs duration of analgesia by nearly 5hrs
    • Decreases time to onset of sensory and motor block by nearly 10mins
    • Effective adjunct in upper limb, lower limb and truncal blocks
    • Not associated with neurotoxicity
    • May be superior to clonidine

  • Downsides:
    • Prolongs duration of motor block by a similar duration
    • Greater benefit from off-license perineural use than traditional IV use
    • Increased risk of hypotension and bradycardia (3x)

  • Synthetic partial MOP and KOP opioid antagonist
  • Perineural effects may be via its mechanism as a voltage-gated sodium channel inhibitor
  • Dose: 2-3μg/kg (e.g. 100 - 300μg/kg)

  • Benefits:
    • Increases the duration of analgesia from bupivacaine and ropivacaine by up to 9hrs
    • Effects seen whether perineural or IM administration
    • Not known to be neurotoxic

  • Downsides:
    • PONV (up to 5x increase if no anti-emetic administered)
    • Pruritus

  • NMDA receptor antagonist
  • Increases the excitation threshold in peripheral nerves
  • May act perineurally by:
    • Its effect on neuronal membrane potential as a positively charged divalent ion
    • Calcium antagonism
  • Dose 150-600mg perineurally

  • Benefits:
    • Prolonged duration of analgesia, with reduced pain scores up to 12hrs post-operatively
    • Effective adjunct across a range of UL, LL and trunk blocks
    • May reduce incidence of PONV
    • Generally safe

  • Downsides:
    • Perineural safety not well established and some concern re: potential neurotoxicity

  • There are a number of postulated mechanisms as to how perineural dexamethasone reduces postoperative pain:
    • Direct inhibition of signal transmission in C-fibres by binding to glucocorticoid receptors on neuronal cell membranes
    • Local vasoconstriction
    • Local anti-inflammatory effect
    • Systemic anti-inflammatory effect following systemic absorption
    • Increased expression of inhibitory potassium channels and therefore educed neuronal excitability
  • Dose: 4-10mg, although lower doses may be as effective as higher doses

  • Benefits:
    • IV or perineural administration can prolong sensory block by 4 - 8hrs
    • IV administration has other benefits e.g. reduction of PONV
    • Not known to cause perineural inflammation or neuronal toxicity itself
    • Non-clinically significant reduction in time to block onset

  • Downsides:
    • Increased mean duration of motor blockade too, although by 2 - 4hrs
    • Preservatives (benzyl alcohol, propylene) can cause neurotoxicity if administered perineurally - need to use preservative-free version
    • Long-term concerns about surgical-site infection and deranged glycaemic control
    • Not compatible with ropivacaine as it can crystallise

Conflicting evidence for perineural use

  • Fentanyl
  • Morphine
  • Tramadol
  • NSAIDs

Lack of demonstrated effectiveness

  • Ketamine
    • Concerns re: neurotoxicity when given perineurally
    • Doesn't reduce post-block rebound pain either, even when given IV (BJA, 2022)

  • Neostigmine: significant adverse effects and neurotoxicity

  • Midazolam: neurotoxicity