Although the principal use of local anesthetics is to achieve anesthesia in a restricted area, these agents are sometimes deliberately administered systemically to take advantage of suppressive effects on pain processing. In addition to documented reductions in anesthetic requirement and postoperative pain, systemic administration of local anesthetics has been used with some success in the treatment of chronic pain, and this effect may outlast the duration of anesthetic exposure. The achievement of pain control by systemic administration of local anesthetics is thought to derive, at least in part, from the suppression of abnormal ectopic discharge, an effect observed at concentrations of local anesthetic an order of magnitude lower than those required for blockade of propagation of action potentials in normal nerves. Consequently, these effects can be achieved without the adverse effects that would derive from failure of normal nerve conduction. Escalating doses of anesthetic appear to exert the following systemic actions: (1) low concentrations may preferentially suppress ectopic impulse generation in chronically injured peripheral nerves; (2) moderate concentrations may suppress central sensitization, which would explain therapeutic benefit that may extend beyond the anesthetic exposure; and (3) higher concentrations will produce general analgesic effects and may culminate in serious toxicity.
Local anesthetic toxicity derives from two distinct processes: (1) systemic effects following inadvertent intravascular injection or absorption of the local anesthetic from the site of administration; and (2) neurotoxicity resulting from local effects produced by direct contact with neural elements.
A. Systemic Toxicity
The dose of local anesthetic used for epidural anesthesia or high-volume peripheral blocks is sufficient to produce major clinical toxicity, even death. To minimize risk, maximum recommended doses for each drug for each general application have been promulgated. The concept underlying this approach is that absorption from the site of injection should appropriately match metabolism, thereby preventing toxic serum levels. However, these recommendations do not consider patient characteristics or concomitant risk factors, nor do they take into account the specific peripheral nerve block performed, which has a significant impact on the rate of systemic uptake (Figure 26–2). Most importantly, they fail to afford protection from toxicity induced by inadvertent intravascular injection (occasionally into an artery, but more commonly a vein).
1. CNS toxicity—All local anesthetics have the ability to produce sedation, light-headedness, visual and auditory disturbances, and restlessness when high plasma concentrations result from rapid absorption or inadvertent intravascular administration. An early symptom of local anesthetic toxicity is circumoral and tongue numbness and a metallic taste. At higher concentrations, nystagmus and muscular twitching occur, followed by tonic-clonic convulsions. Local anesthetics apparently cause depression of cortical inhibitory pathways, thereby allowing unopposed activity of excitatory neuronal pathways. This transitional stage of unbalanced excitation (ie, seizure activity) is then followed by generalized CNS depression. However, this classic pattern of evolving toxicity has been largely characterized in human volunteer studies (which are ethically constrained to low doses) and by graded administration in animal models. Deviations from such classic progression are common in clinical toxicity and will be influenced by a host of factors, including patient vulnerability, the particular anesthetic administered, concurrent drugs, and rate of rise of serum drug levels. A recent literature review of reported clinical cases of local anesthetic cardiac toxicity found prodromal signs of CNS toxicity in only 18% of cases.