Local anesthetic toxicity

Main article: Local anesthetic

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. Small doses of local anesthetic to achieve an adequate level of anesthesia may lead to eventual administration of toxic doses. Harm from anesthesia is not very common and only occurs with large doses.
2. Injection of anesthesia in a confined space may result in excessive 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.

Toxicity

Localized

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 as lidocaine, and prilocaine. It is also a metabolic by-product of pramod methylparaben, a preservative in multi-dose vials of lidocaine. 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.

Use of topical anesthetics for relief of eye pain can result in severe corneal damage. See abuse of anesthetics for ocular pain relief page.

Systemic

Systemic toxicity of local anesthetics can be described by the direct effects on the immune system, blood (hematologic), central nervous system, and cardiovascular system.

Immune system

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

Hematologic

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.

Central Nervous System

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.

Cardiovascular

Cardiovascular effects are primarily those of direct myocardial depression and bradycardia, which may lead to cardiovascular collapse. At extremely high levels, cardiac arrhythmia or hypotension and cardiovascular collapse occur.

Management

Intravenous lipid emulsions may be useful for cardiotoxicity; however, the evidence at this point is still limited.

This treatment is termed lipid rescue. This method of toxicity treatment was invented by Dr. Guy Weinberg in 1998, and had not been widely used until after the first published successful rescue in 2006. Since then more than a dozen case reports have been published. Recently, lipid therapy held the cover of the May 2008 issue of Anesthesia & Analgesia, where the bulk of the issue had to do with this life saving technique.

Though most reports to date have used Intralipid, a commonly available intravenous lipid emulsion, other emulsions, such as Liposyn and Medialipid have also been shown to be effective.

There is ample supporting animal evidence and human case reports of successful use in this way. In the UK, efforts have been made to publicise this use more widely and lipid rescue has now been officially promoted as a treatment by the Association of Anaesthetists of Great Britain and Ireland. There is now one published case report of successful treatment of refractory cardiac arrest in bupropion and lamotrigine overdose using lipid emulsion.

The design of a 'homemade' lipid rescue kit has been described

Although lipid rescue mechanism of action is not completely understood, it may be that the added lipid in the blood stream acts as a sink, allowing for the removal of lipophilic toxins from affected tissues. This theory is compatible with two studies on lipid rescue for clomipramine toxicity in rabbits and with a clinical report on the use of lipid rescue in veterinary medicine to treat a puppy with moxidectin toxicosis.

External links

• University of Illinois at Chicago Department of Anesthesiology
• The American Society of Regional Anesthesia
• Regional Anesthesia and Pain & Medicine
• Lipid Rescue