What factor significantly influences the duration of local anesthesia?

The duration of local anesthesia is significantly influenced by the degree of protein binding ability of the anesthetic agent. Anesthetic agents that have a high affinity for proteins tend to remain in an active form longer within the tissues, which can prolong their effect. When an anesthetic binds to proteins in the tissue, it is less available for diffusion away from the site of action, thereby extending the duration of anesthesia.

While concentration, time of administration, and route of administration are also important factors regarding the efficacy and onset of anesthesia, protein binding specifically relates to how long the anesthetic will exert its effect once administered. Higher protein binding means more sustained release of the anesthetic, contributing to an extended duration of action. Thus, among the options presented, the degree of protein binding ability is a critical determinant of how long the anesthetic will work.