Local Anesthetic Toxicity

While generally safe, local anesthetic agents can be toxic if used in excessive doses or administered improperly. Even when administered properly, patients may still experience unintended reactions to local anesthetics.

Excessive doses may be unintentionally administered in several ways.
 * 1) Repetitive (small) doses of local anesthetic to achieve an adequate level of anesthesia may lead to eventual adminitration of toxic doses.
 * 2) Injection of anesthesia in a confined space may result in excesive fluid pressure that may damage nerves.
 * 3) Doses intended for epidural or intra-support-tissue administration may be accidentally delivered as intravascular injection resulting in accelerated systematic absorption.

The toxic effects of local anesthetics can be classified by localized and systemic effects.

Localized toxicity
The local adverse effects of anesthetic agents include neurovascular manifestations such as prolonged anesthesia (numbness) and paresthesia (tingling, feeling of "pins and needles", or strange sensations). These are symptoms of localized nerve damage.

Risks
Symptoms lasting more than one week happen in between 1 and 5 out of every 100 nerve blocks (1–5%). The risk varies between the different locations and types of nerve blocks.

Recovery
Permanent nerve damage after a peripheral nerve block is rare. Symptoms are very likely to resolve within a few weeks. The vast majority of those affected (92–97%), recover within four to six weeks. 99% of these people have recovered within a year. It is estimated that between 1 in 5,000 and 1 in 30,000 nerve blocks result in some degree of permanent persistent nerve damage.

It is suggested that symptoms may continue to improve for up to 18 months following injury.

Causes
Causes of localized symptoms include:
 * 1) neurotoxicity due to allergenic reaction,
 * 2) damage to the nerve due to excessive fluid pressure, or
 * 3) severing of nerve fibers and support tissue with the needle.

A cause of local toxicity is allergic reaction to para-aminobenzoic acid (PABA). These reactions range from urticaria to anaphylaxis.

PABA is a metabolic product of the degradation of Ester class of local anesthetics, such as Procaine (Novocaine), Benzocaine, and, to a lesser degree, amide class anesthetics such asLidocaine, and Prilocaine. It is also a metabolic by-product of Methylparaben, a preservative in multi-dose vials of Lidocane. When allergic response to injected anesthetics does occur, it is most likely due to the ester class local anesthetics. The amide class of local anesthetics is far less likely to produce allergic reaction. .

Systemic Toxicity
Systemic toxicity of anesthetics involves the central nervous system (CNS), the cardiovascular system, and the immune system.

It can be described by the direct effects on the immune system, blood (hematologic), and cardiovascular system.

Immune System Effects
As noted previously, allergic reaction to metabolic break-down of anesthetic agents and preservatives (PABA) can cause anaphylaxis.

Hematologic Effects
Methemoglobinemia is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces cyanosis and symptoms of hypoxia. Benzocaine, Lidocaine, and Prilocaine all produce this effect, especially Benzocaine.

Cardiovascular Effects
Cardiovascular effects are primarily those of direct myocardial depression and bradycardia, which may lead to cardiovascular collapse. .

Systemic toxic reactions to locally administered anesthetics are progressive as the level of the anesthetic agent in the blood rises. Initial symptoms suggest some form of central nervous system excitation such as a ringing in the ears (tinnitus), a metallic taste in the mouth, or tingling or numbness of the mouth. advanced symptoms include motor twitching in the periphery followed by grand mal seizures, coma, and eventually respiratory arrest. At extremely high levels, cardiac arrhythmia or hypotension and cardiovascular collapse occur.