The chance discovery, however, that lipid emulsions can help reverse catastrophic cardiovascular collapse, has led to clinical awareness and the establishment of guidelines for the use of lipid emulsions in the treatment of severe cardiovascular toxicity from local anesthesia. Treatment options are traditionally based on cardiovascular support, including fluids, vasopressors, and inotropes, in addition to securing the airway and controlling central nervous system toxicity including seizures. The advent of ultrasound guided regional anesthesia may further improve safety by the visualization of anesthetic solution spread with injection, though this has yet to be fully tested in clinical trials. Most anesthesiologists will be familiar with practice guidelines for safe regional anesthesia, which include an estimate of maximal dose, establishment of intravenous access, adequate monitoring, access to resuscitation equipment, aspiration prior to injection, and thorough patient evaluation to determine factors that may influence absorption and biotransformation.

Both drugs are marketed as safer than bupivacaine on the basis of animal studies.Īvoiding local anesthetic toxicity is primarily based on good practice, and secondly on treating toxicity once it has occurred. The S(−) enantiomer of bupivacaine was also found to be more potent 3 and less cardiotoxic than the R(+) enantiomer 4 leading to the selection of the S(−) enantiomer, levobupivacaine, as a safer alternative to bupivacaine. Ropivacaine is produced as the S(−) enantiomer only, as some studies have suggested a decrease in toxicity associated with the S(−) enantiomer when compared to the racemate. The amino amide ropivacaine, a derivative of mepivacaine, was introduced in 1996 as the safest long acting local anesthetic.

2 This led to a search for long acting local anesthetics with improved therapeutic margins, in order to reduce the risk of death in the event of accidental (usually intravenous) overdose. This gave rise to (chronologically) mepivacaine, prilocaine, bupivacaine, etidoacaine and articaine being developed in to the 1970s.Īfter the introduction of bupivacaine, it became apparent that accidental overdose was often fatal, and responded poorly to conventional resuscitation methods. 1 Since lidocaine, local anesthetic agents have been designed by integrating on to the amide motif. This led to a substitution of the local amide ring to produced lidocaine in 1944 which was introduced into clinical practice in 1948. Nirvaquine experienced very limited use however due to its local irritant properties. Tetracaine was the last ester type local anesthetic developed in 1930, but is no longer used clinically.Īmide anesthetics became the next major development pathway, stemming from nirvaquine which was synthesized in 1898. Procaine use has become confined to infiltration anesthesia as it has demonstrated low potency, slow onset, short duration and low ability to infiltrate tissue. Amino ester local anesthetics were developed in the early 1900s producing benzocaine in 1900 and procaine in 1905. The need for a local anesthetic with reduced toxicity led to the development of numerous compounds. The common practice of treating cocaine toxicity with barbiturates did not help in reducing cocaine-related deaths. Along with increasing use in clinical settings, the toxicity of cocaine became apparent almost simultaneously with the incidence of central nervous system and cardiovascular system toxicity increasing parallel to its use.

After isolation of the main alkaloid in cocaine by Neimann in 1860, Ritter von Schroff described its use as a narcotic, and Percy was the first to propose its use as a topical local anesthetic in 1856. Topical application of agents which essentially ‘numb’ have been used since the introduction of the Peruvian compound known as khoka to Europe in the early 1500’s where it became commonly known as cocaine.

First lipid emulsion therapy used