Which factor affects the efficacy and onset of local anesthetics during anesthesia?

The efficacy and onset of local anesthetics are significantly influenced by pH, which impacts the drug's ionization and, consequently, its ability to penetrate nerve membranes. Local anesthetics are weak bases, and their ionization is highly dependent on the local pH of the tissue where they are administered.

In a more alkaline environment, a greater proportion of the local anesthetic remains in its uncharged (non-ionized) form. The non-ionized form is lipid-soluble, allowing it to readily cross the nerve membrane and reach its site of action at the sodium channels. Conversely, in more acidic environments, which may occur due to inflammation or infection, there is increased ionization of the anesthetic. This results in a reduced amount of non-ionized drug available to penetrate the nerve membrane, which delays the onset and diminishes the effectiveness of anesthesia.

While temperature, pressure, and volume of the local anesthetic may have their own effects on various aspects of anesthetic use, pH specifically alters the chemical state of the drug, making it a critical factor in determining how effectively a local anesthetic will work in a clinical setting.