2016A06 Discuss the factors influencing the speed of onset of blockade, of a
major peripheral nerve, with local anaesthetic.



·      Intro

·      Rate of passage: factors increasing it

·      MLAC: factors decreasing it



Local anaesthetic

·  Antagonist at axonal voltage-gated Na+ channel (VDNaC)

Drug path

·  Interstitium -> axoplasm

·  Only unionised drug diffuses readily

·  Ionised > unionised drug enters receptor

·  ICF > ECF drug enters receptor

Determinants of speed of onset

1.Rate of passage into axoplasm

2.Minimum local analgesic concentration (MLAC)


1.Rate of passage (factors accelerating it):

Fick’s law




↑Tissue protein binding


↑Volume injected


·  ↑Size of nerve (e.g. sciatic cf. median)

·  ↑Connective tissue (e.g. sciatic cf. median)

o Added hyaluronidase -> ↓effective thickness

·  ↓Distance from centre of bundle (i.e. proximal affected before distal)

↑Diffusion coeff

·  ↑% unionised: **most important factor

o Drug: e.g. prilocaine 33% cf. bupivacaine 15%

o Additive: e.g. HCO3- -> ↑% unionised

o Patient: e.g. abscess -> acidosis -> ↓↓% unionised

·  ↑Lipid solubility (e.g. bupiv 1000x cf. lignocaine 150x)

·  ↓Molecular weight


2.MLAC (factors decreasing it = factors increasing sensitivity):

Nerve sensitivity

·  Myelination (must block 3 consecutive nodes of Ranvier 1cm)

·  ↑Frequency of action potential

·  ↓Nerve diameter -> ↑ratio surface area : axon unit volume


Order of decreasing sensitivity: B > C > Aδ > Aγ > Aβ > Aα (sensory 2x motor)


·  ↑Tissue pH

·  Pregnancy


·  ↑Potency (e.g. ropiv 40% less than bupiv)
(correlates with ↑lipid solubility)


·  Opioid

·  α2 agonist


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