2017B08 Discuss the factors affecting duration of action of a local anaesthetic
block to a major peripheral nerve.



·      Intro

·      Max concentration

·      Rate of removal

·      MLAC



Local anaesthetic

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

Drug path

·  Axoplasm -> interstitium -> plasma

·  Only unionised drug diffuses readily

Determinants of rate of offset

1.   Maximum concentration in axoplasm

2.   Rate of removal from axoplasm

3.   Minimum local analgesic concentration (MLAC)


1.Maximum concentration (factors increasing it)

·         ↑Concentration of solution

·         ↑Volume injected


2.Rate of removal (factors slowing it):

Fick’s law


·  ↑VDNaC affinity -> ↓dwell time (e.g. bupiv)

·  ↑Tissue protein binding (e.g. bupiv) **most important factor



·  Intrinsic vasoconstriction (e.g. ropiv constrict cf. lignocaine dilate)

·  Added adrenaline

·  Slow metabolism -> slow removal (e.g. amidase cf. plasma cholinesterase)


·  Low intrinsic blood flow (decreasing order: tracheal / intercostal / caudal / paracervical / epidural / plexus / peripheral nerve / subcut) *

·  Tissue hypoperfusion (↓ if heart failure, shock; ↑if pregnancy, neonate)

·  Slow metabolism (e.g. neonate)




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

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

·  ↓Distance from centre of bundle (i.e. distal cf. proximal target)

↓Diffusion coeff (minor)

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

·  ↑Molecular weight

·  ↓% unionised (e.g. bupiv 15% cf. lignocaine 25%); or ↓tissue pH


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

Nerve sensitivity

·  Myelination (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 (ropiv 8x ligno 2x)
(correlates with ↑lipid solubility)


·  Opioid

·  α2 agonist


Feedback welcome at ketaminenightmares@gmail.com