Anesthetics local, neurotoxicity

The two major forms of local anesthetic toxicity are (1) systemic effects following absorption of the local anesthetic from their site of administration and (2) direct neurotoxicity from the local effects of these drugs when high concentrations are administered in close proximity to the spinal cord and other major nerve trunks. When blood levels of local anesthetics rise rapidly, adverse effects on several major organ systems may be observed. 

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Two major forms of local anesthetic toxicity are recognized direct neurotoxicity from the local effects of certain agents administered around the cord or other major nerve trunks, and systemic... 

When applied at excessively high concentrations, all local anesthetics can be toxic to nerve tissue. Chloroprocaine and lidocaine appear to be more neurotoxic than other local anesthetics when used... 

Nerve injuries are well recognized complications of regional anesthesia (Selander 1993 Borgeat Ekatodramis 2001). Kalichman et al. (1986, 1988, 1998) studied neurotoxicity of local anesthetics in rat sciatic nerve. 

Selander D (1993) Neurotoxicity of local anesthetics animal data. Reg Anesth 18 461-468... 

The use of benzyl alcohol as a local anesthetic was previously discussed. It is also used as a preservative in parenteral dosage forms. However, there is some evidence that benzyl alcohol is neurotoxic and its use is contraindicated in the United Kingdom in children under 3 years of age. ° ... 

The importance of the patient s position has been illustrated by a study in which transient neurological symptoms occurred in five of 12 volunteers who were given 5% lidocaine 50 mg intrathecaUy and then placed in the low lithotomy position (251). No consistent abnormalities were detected by prespinal and postspinal electromyography, nerve conduction studies, or somatosensory evoked potentials. This is in line with the current opinion that transient neurological symptoms constitute neither a true neurological syndrome nor an expression of the neurotoxicity of local anesthetics. 

Several explanations for the increased neurotoxicity of vasoconstrictors, such as adrenaline and phenylephrine, in combination with local anesthetics have been offered ... 

A high concentration of tetracaine given intrathecally in rabbits caused neuronal injury and glutamate release in the CSF (254). The authors postulated that this might give some insight into the mechanisms of neurotoxicity of intrathecal local anesthetics. 

Radwan lA, Saito S, Goto F. The neurotoxicity of local anesthetics on growing neurons a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesth Analg 2002 94(2) 319-24. 

It has been suggested that sodium bisulfite, a preservative in phenylephrine solutions for injection, may have been responsible for transient neurological symptoms that have been observed in some patients (7). However, the original authors rejected this, since the dose of bisulfite was small and since there is uncertain evidence whether the compound is neurotoxic in any case. Another correspondent commented that tetracaine itself may be more toxic than other local anesthetics the authors did not address this point in their reply (8). 

Local tissue reactions, including inflammation and necrosis, can occur, particularly if local anesthetic formulations containing epinephrine (adrenaline) have been administered. Allergic reactions can also occur and are most commonly associated with the esters (e.g. procaine, see Ch. 2). Neurotoxicity is rare but may occur when 200 ml or more of a local anesthetic is administered by infiltration in a short period. It is more likely that a horse will become ataxic, which can lead to selftrauma, after nerve blockade in the limbs, and severe hindlimb ataxia can follow the caudal... 

When local anesthetics are to be administered spinally or for regional blocks they should be preservative-free saline preparations as the neurotoxicity of preservatives and excipiants generally have not been systematically studied. 

Sakura S, Bollen AW, Ciriales R, Drasner K (1995) Local anesthetic neurotoxicity does not result from blockade of voltage-gated sodium channels. Anesth Analg 81 338-346... 

An allergic reaction to specific agents is an obvious contraindication. Allergy to para-aminobenzoic acid (PABA) is a contraindication to use of ester local anesthetics due to the fact that PABA is a metabolic product of ester metabolism. Methylparaben is a common preservative chemically similar to PABA and likewise can cause an allergic reaction. Metabisulfite is a commonly used preservative that may also cause allergic reactions but more notably is neurotoxic when used intrathecally. Local anesthetics containing any preservative should not be used intrathecally. Ester local... 

Because liposomes come in different shapes and sizes, the performance of each varies with their structure. The liposomes that will carry analgesics should fulfill certain criteria, including but not limited to sterility, no neurotoxicity, no adverse effects, structural stability, and lengthened duration of action from the current standard [1]. While most liposomal local anesthetics are still being tested in humans, animal... 

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