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British Journal of Anaesthesia, 1989, Vol. 63, No. 4 444-452
© 1989 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

STRUCTURE—ACTIVITY RELATIONSHIPS IN DIFFERENTIAL NERVE BLOCK AT HIGH AND LOW FREQUENCY STIMULATION

J. A. W. WILDSMITH, M.D., F.F.A.R.C.S., D. T. BROWN, F.F.A.R.C.S., D. PAUL, F.F.A.R.C.S. and S. JOHNSON

Department of Anaesthetics, The Royal Infirmary Edinburgh EH3 9YW

Correspondence to J.A.W.W.

We have examined the in vitro sensitivities of A, B and C fibres in rabbit vagus nerves to local anaesthetic block with a range of local anaesthetic drugs. The nerves were maintained at 37°C and pH 7.4 using an electrolyte solution equilibrated with 5% carbon dioxide. A fibres were the most, and C fibres the least, sensitive to block at low frequency stimulation (0.0167 Hz). Equipotent concentrations of the various drugs blocked C fibres at approximately the same rate. Rate of A fibre block was related to physico-chemical properties of individual drugs. Low pKa and high lipid solubility favoured block of A fibres before C, whereas the reverse was true for high pKa and low solubility. Absolute potency was related to lipid solubility, but each type of local anaesthetic drug in clinical use has a different inherent potency. With stimulation at high frequencies (20 and 40 Hz), C fibres were more sensitive to use-dependent block than A fibres; this effect was more marked with drugs containing an amide than an ester linkage. Molecular size and lipid solubility may inter-react to govern the ability to produce use dependent block. Agents which contain an amide linking group, have a high pKa and are of low lipid solubility, may be used to produce differential C fibre block.


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