What factor can significantly enhance the effectiveness of local anesthetics?

Increasing the pH of the local anesthetic solution significantly enhances its effectiveness because local anesthetics exist in two forms: ionized and non-ionized. The non-ionized form is the active form that can cross cell membranes and provide anesthesia. When the pH of the solution is raised (making it more alkaline), a larger proportion of the anesthetic exists in this non-ionized state, allowing it to penetrate nerve membranes more effectively and subsequently leading to improved efficacy.

In contrast, reducing the volume of the anesthetic might limit the area of tissue that can be affected, potentially reducing the overall effectiveness. Using a thicker solution could cause difficulties in delivery and may not necessarily correlate with increased effectiveness. Cooling the anesthetic could potentially slow nerve conduction but might not improve the anesthetic's effectiveness itself. Hence, enhancing the pH is the most beneficial adjustment that directly improves the function of local anesthetics.