Toxicity of local anesthetics

Systemic neurotoxicity due to excessive cerebral local anesthetic blood levels is one of the most severe and most frequent adverse outcome of local anesthetic use. Toxic levels are most often produced by unintentional intravenous or intraarterial injection(1,2). Toxicity can also result from the rapid absorption of drug following perineural injection. Peak blood levels are usually obtained according to the injection site after 20-40 min. The neurotoxic symptoms are seen in roughly the same progression and proportion with all local anesthetics. The first symptoms are numbness of tongue and lightheadedness followed by visual disturbance, muscular twitching, unconsciousness and ending in convulsions and coma(3,4). The physiopathology is explained by a imbalance between inhibitatory and excitatory pathways within the central nervous system. The GABA systeminhibitory – is blocked by high local anesthetic brain levels. The local anesthetics themselves do not produce direct permanent damage to the central nervous system. The depression reverses rapidly as the blood levels fall below the seizure threshold. The major risk to the patient is from cerebral hypoxia during the period of seizures and coma. Hypoxemia is rapid in onset because of the severe muscle activity in conjunction with apnea. Treatment logically consists of oxygenation and support until the blood levels are lowered by redistribution of the drug. Midazolam and propofol are the most useful drugs to treat convulsions induced by local anesthetics(5,6). Both are GABA-agonists and are therefore able to restore a balance between inhibitory and excitatory pathways(7,8). However, propofol may be preferred because of its more favorable pharmacokinetic/pharmacodynamic profile. Several factors influence the actual seizure threshold in a given individual. Any factor that interferes with normal plasma clearance (such as liver failure for the amino esters) will greatly increase the expected toxicity. Hypercarbia as well as metabolic acidosis also will lower the seizure threshold for all drugs. Fortunately central nervous system hyperexcitability can be managed quickly and easily.