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Therapeutic duration of traditional local anesthetics when used in peripheral nerve blocks is normally limited. This article describes novel approaches to extend the duration of peripheral nerve blocks currently available or in development. Three newer approaches on extending the duration of peripheral nerve blocks include site-1 sodium channel blockers, novel local anesthetics delivery systems, and novel adjuvants of local anesthetics. Compared with plain amide-based and ester-based local anesthetics, alternative approaches show significant promise in decreasing postoperative pain, rescue opioid requirement, hospital length-of-stay, and overall health care cost, without compromising the established safety profile of traditional local anesthetics.

Since the public demonstration of ether as a novel, viable anesthetic for surgery in 1846, the field of anesthesia has continually sought the ideal anesthetic-rapid onset, potent sedation-hypnosis with a high therapeutic ratio of toxic dose to minimally effective dose, predictable clearance to inactive metabolites, and minimal side effects. This article aims to review current progress of novel induction agent development and provide an update on the most promising drugs poised to enter clinical practice. In addition, the authors describe trends in novel agent development, implications for health care costs, and implications for perioperative care.