2016A Question 06

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

Examiner Report

72% of candidates achieved a pass in this question.

This question required three key areas to be addressed.

Firstly, the speed of onset of a clinical nerve blockade was expected to be discussed in terms of drug effects such as diffusion into the nerve, crossing the cell membrane to have an effect, and the binding to the sodium channel inside the cell.

The pharmacokinetic principles outlined in Fick’s Law were an essential requirement to obtain a pass in this question. The answer did, however, need to be specific to local anaesthetics and onset – not just a generic listing of factors in the equation & inclusion of irrelevant factors such as duration of action or plasma circulation.

In a significant proportion of answers there was incorrect information & understanding with regard to the role of lipid solubility in the onset of effect of the local anaesthetics. Generally, the effects of pKa and ionization were correctly stated. Extra credit was given for the inclusion of correct values of the different common local anaesthetics.

Secondly, discussion of major peripheral nerve characteristics was required for a higher scoring answer. It was expected to include the structure and function of peripheral nerves and the influence of these factors on speed of onset. Answers that discussed subarachnoid blocks or epidurals could not be scored.

Including information about patient characteristics also achieved higher marks. The altered physiological states such as pregnancy, the area of injection and closeness to the nerve and conditions such as diabetes and old age were given credit as they indicated a broader understanding of the topic.

Thirdly, the drugs themselves needed to be addressed. Factors such as dose and concentration were simple factors that were often overlooked in answers. Also, the influence of tissue pH such as with infection was expected.

The poorly scoring answers lacked the details required to cover all aspects of the question, while some discussed irrelevant details related to duration of effect, metabolism, the use of vasoconstrictors & protein binding. Simply not addressing nerve factors or clinical factors meant candidates missed scoring valuable points for a pass.

Model Answer


  • Introduction
  • Rate of passage: Factors increasing it
  • Minimum Local Anaesthetic Concentration (MLAC): Factors decreasing it


Term Definition
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)

Rate of Passage

Factor Drug transfer ↑ with:
Fick’s Law
↑ C1 ↑ Concentration
↓ C2 ↑ Tissue protein binding
↑ Area ↑ Volume injected
↓ Thickness

- ↑ Size of nerve (e.g. Sciatic cf. median)

- ↑ Connective tissue (e.g. Sciatic cf. median)

 - Added hyaluronidase → ↓ Effective thickness

- ↓ Distance from centre of bundle (i.e. Proximal affected before distal)

↑ Diffusion coeff

- ↑ % Unionised (most important factor):

 - Drug: e.g. Prilocaine 33% cf. bupivacaine 15%

 - Additive: e.g. HCO3- → ↑ % Unionised

 - Patient: e.g. Abscess → Acidosis → ↓↓ % Unionised

- ↑ Lipid solubility (e.g. Bupiv 1000x cf. lignocaine 150x)

- ↓ Molecular weight

Minimum Local Anaesthetic Concentration (factors decreasing it = factors increasing sensitivity)

Factor MLAC ↓ with/Sensitivity ↑ with:
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

Last updated 2021-08-23

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