2. Transient neurologic symptoms (TNS)—In addition to the very rare but devastating neural complications that can occur with neuraxial (spinal and epidural) administration of local anesthetics, a syndrome of transient pain or dysesthesia, or both, has been recently linked to use of lidocaine for spinal anesthesia. Although these symptoms are not associated with sensory loss, motor weakness, or bowel and bladder dysfunction, the pain can be quite severe, often exceeding that induced by the surgical procedure. TNS occurs even at modest doses of anesthetic and has been documented in as many as one third of patients receiving lidocaine, with increased risk associated with certain patient positions during surgery (eg, lithotomy) and with ambulatory anesthesia. Risk with other anesthetics varies considerably. For example, the incidence is only slightly reduced with procaine or mepivacaine but appears to be negligible with bupivacaine, prilocaine, and chloroprocaine. The etiology and significance of TNS remain to be established, but differences between factors affecting TNS and experimental animal toxicity argue strongly against a common mechanism mediating these symptoms and persistent or permanent neurologic deficits. Nonetheless, the high incidence of TNS has greatly contributed to dissatisfaction with lidocaine as a spinal anesthetic, leading to its near abandonment for this technique (although it remains a popular and appropriate anesthetic for all other applications, including epidural anesthesia). Chloroprocaine, once considered a more toxic anesthetic, is now being explored for short-duration spinal anesthesia as an alternative to lidocaine, a compound that has been used for well over 50 million spinal anesthetic procedures.
Approved for use in the USA as a dental anesthetic in April 2000, articaine is unique among the amino-amide anesthetics in having a thiophene, rather than a benzene ring, as well as an additional ester group that is subject to metabolism by plasma esterases (Table 26–1). The modification of the ring serves to enhance lipophilicity, and thus improve tissue penetration, while inclusion of the ester leads to a shorter plasma half-life (approximately 20 minutes), potentially imparting a better therapeutic index with respect to systemic toxicity. These characteristics have led to widespread popularity in dental anesthesia, where it is generally considered to be more effective, and possibly safer, than lidocaine, the prior standard. Balanced against these positive attributes are concerns that development of persistent paresthesias, while rare, may be three times more common with articaine. However, prilocaine has been associated with an even higher relative incidence (twice that of articaine). Importantly, these are the only two dental anesthetics that are formulated as 4% solutions; the others are all marketed at lower concentrations (eg, the maximum concentration of lidocaine used for dental anesthesia is 2%), and it is well established that anesthetic neurotoxicity is, to some extent, concentration-dependent. Thus, it is quite possible that enhanced risk derives from the formulation rather than from an intrinsic property of the anesthetic. In a recent survey of US and Canadian dental schools, over half of respondents indicated that 4% articaine is no longer used for mandibular nerve block.
As previously noted, benzocaine’s pronounced lipophilicity has relegated its application to topical anesthesia. However, despite over a century of use for this purpose, its popularity has recently diminished owing to increasing concerns regarding its potential to induce methemoglobinemia. Elevated levels can be due to inborn errors or can occur with exposure to an oxidizing agent, and such is the case with significant exposure to benzocaine (or nitrites, see Chapter 12). Because methemoglobin does not transport oxygen, elevated levels pose serious risk, with severity obviously paralleling blood levels.