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)

· ↑Concentration of solution

· ↑Volume injected

Fick’s law
↓C₁	· ↑VDNaC affinity -> ↓dwell time (e.g. bupiv) · ↑Tissue protein binding (e.g. bupiv) **most important factor
↑C₂	Drug: · Intrinsic vasoconstriction (e.g. ropiv constrict cf. lignocaine dilate) · Added adrenaline · Slow metabolism -> slow removal (e.g. amidase cf. plasma cholinesterase) Patient: · 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)
↓Area
↑Thickness	· ↑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

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)
Patient	· ↑Tissue pH · Pregnancy
Drug	· ↑Potency (ropiv 8x ligno 2x) (correlates with ↑lipid solubility)
Additives	· Opioid · α₂ agonist