Local anes onset: Factors influencing

The onset of local anesthetics are dependent on the anesthetic technique utilized. The shortest onset time is encountered after intrathecal or subcutaneous administration, the longest occurs with peripheral nerve blocks. Variations are due to anatomy and amount of drug utilized. Brachial plexus block is slow since the agent is injected some distance from nerve roots and must diffuse through various tissues before reaching the nerve membrane.

At the level of the nerve nerve, the onset is correlated with pKa of the various local anesthetics and lipid solubility. The pKa determines ionization and ionization influences diffusion of anesthetics across the nerve sheath and membrane with the uncharged base form diffusing more quickly than the charged cationic form. The closer to physiologic pH that the pKa is, the more anesthetic exists in the uncharged base form. With the exception of benzocaine, the pKa’s of all local anesthetics are greater than tissue pH (7.4). Lower pKa results in a more rapid onset. Onset is also reduced by increasing the solution pH.

Onset can also be shortened by increasing the concentration or dose. Chloroprocaine, despite having a pKa of 9, has a rapid onset because of its use in high (as high as 3%) concentrations.