Although structurally similar to bupivacaine and ropivacaine (Table 26–1), mepivacaine displays clinical properties that are comparable to lidocaine. However, it differs from lidocaine with respect to vasoactivity, as it has a tendency toward vasoconstriction rather than vasodilation. This characteristic likely accounts for its slightly longer duration of action, which has made it a popular choice for major peripheral blocks. Lidocaine has retained its dominance over mepivacaine for epidural anesthesia, where the routine placement of a catheter negates the importance of a longer duration. More importantly, mepivacaine is slowly metabolized by the fetus, making it a poor choice for epidural anesthesia in the parturient. When used for spinal anesthesia, mepivacaine has a slightly lower incidence of TNS than lidocaine.
Prilocaine has the highest clearance of the amino-amide anesthetics, imparting reduced risk of systemic toxicity. Unfortunately, this is somewhat offset by its propensity to induce methemoglobinemia, which results from accumulation of one of its metabolites, ortho-toluidine, an oxidizing agent. As a spinal anesthetic, prilocaine’s duration of action is slightly longer than that of lidocaine, and the limited data suggest it carries a low risk of TNS. It is gaining increasing use for spinal anesthesia in Europe, where it has been marketed specifically for this purpose. No approved formulation exists in the USA, and there is no formulation that would be appropriate to use for spinal anesthesia as an off-label indication.
Ropivacaine is an S(–) enantiomer in a homologous series that includes bupivacaine and mepivacaine, distinguished by its chirality and the propyl group off the piperidine ring (Table 26–1). Its perceived reduced cardiotoxicity has led to widespread use for high-volume peripheral blocks. It is also a popular choice for epidural infusions for control of labor and postoperative pain. Although there is some evidence to suggest that ropivacaine might produce a more favorable differential block than bupivacaine, the lack of equivalent clinical potency adds complexity to such comparisons.
The term eutectic is applied to mixtures in which the combination of elements has a lower melting temperature than its component elements. Lidocaine and prilocaine can combine to form such a mixture, which is marketed as EMLA (Eutectic Mixture of Local Anesthetics). This formulation, containing 2.5% lidocaine and 2.5% prilocaine, permits anesthetic penetration of the keratinized layer of skin, producing localized numbness. It is commonly used in pediatrics to anesthetize the skin prior to venipuncture for intravenous catheter placement.
The provision of prolonged analgesia or anesthesia, as in the case of postoperative pain management, has traditionally been accomplished by placement of a catheter to permit continuous administration of anesthetic. More recently, efforts have focused on drug delivery systems that can slowly release anesthetic, thereby providing extended duration without the drawbacks of a catheter. Sustained-release delivery has the potential added advantage of reducing risk of systemic toxicity. Preliminary work encapsulating local anesthetic into microspheres, liposomes, and other microparticles has established proof of concept, although significant developmental problems, as well as questions regarding potential tissue toxicity, remain to be resolved.
It has been clearly demonstrated that anesthetic neurotoxicity does not result from blockade of the voltage-gated sodium channel. Thus, effect and tissue toxicity are not mediated by a common mechanism, establishing the possibility of developing compounds with considerably better therapeutic indexes. In addition, a neosaxitoxin, a site 1 sodium channel biotoxin, is currently being explored as a method to provide prolonged block, with the goal of obviating the need for catheter placement and continuous anesthetic infusion.