Long-Acting Local Anesthetic Agents and Additives: Snake Oil, Voodoo, or the Real Deal?

The onset, spread, density, and duration of a nerve block are functions of what local anesthetic drug is injected, where it is injected, and for how long the nerve is exposed to it. Over the past 27 or more years, as far back as 1988 [1], researchers and companies, initially with topical tetracaine [1], and later as injectable liposomal bupivacaine [2], have been searching for the “magic bullet” to be injected somewhere near a nerve, or infiltrated into tissue, that will eliminate a patient's acute or perioperative pain for as long as the pain lasts without unwanted side effects. The work of the Williams and colleagues, reported in this edition of Pain Medicine , is a further report on such efforts [3–5]. Although we have no or very little evidence of this, which points to a bigger problem eluded upon below, we instinctively know that most pain, especially surgical pain, outlasts our single-injection blocks, and we also know that we have to offer patients nerve blocks that last at least as long as the pain does without causing discomfort and unwanted side effects. Over the years, the challenge of developing a blocking drug that lasts long enough to outlast pain but that does not have similarly long-lasting unwanted side effects has been addressed by combining different drugs and developing new presentations of drugs. Few adjuvant agents, other than perhaps dexamethasone, have stood the test of time [6]. Another attempt was to add epinephrine to the existing arsenal of drugs [7] to cause vasoconstriction and decreased blood flow, thus slowing down the washout of the drugs and increasing the time that the nerve is exposed to the local anesthetic agent. We now know, that epinephrine does not increase the duration of action of bupivacaine or ropivacaine …