Lidocaine neurotoxicity

Once absorbed, foreign compounds may react with plasma proteins and distribute into various body compartments. In both neonates and elderly human subjects, both total plasma-protein and plasma-albumin levels are decreased. In the neonate, the plasma proteins may also show certain differences, which decrease the binding of foreign compounds, as will the reduced level of protein. For example, the drug lidocaine is only 20% bound to plasma proteins in the newborn compared with 70% in adult humans. The reduced plasma pH seen in neonates will also affect protein binding of some compounds as well as the distribution and excretion. Distribution of compounds into particular compartments may vary with age, resulting in differences in toxicity. For example, morphine is between 3 and 10 times more toxic to newborn rats than adults because of increased permeability of the brain in the newborn. Similarly, this difference in the blood-brain barrier underlies the increased neurotoxicity of lead in newborn rats. 

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... 

Kirihara et al. (2003) compared neurotoxicity of intrathecal and epidural lidocaine in rats. 

Kirihara et al. (2003) compared neurotoxicity of intrathecal and epidural lidocaine in rats. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital (30 mg/kg i.p.) and 1.5% halothane. A catheter of stretched polyethylene tubing PE-10 was introduced into the subarachnoid or epidural space using an aseptic technique. Catheters were passed through the L4-L5 intervertebral space and advanced 1.3 cm in the caudal direction. Rats were allowed 4 days to rest for recovery from the operation. 

Kirihara Y, Saito Y, Sakura S et al. (2003) Comparative neurotoxicity of intrathecal and epidural lidocaine in rats. Anesthesiology 99 961-968... 

PROCAINAMIDE LIDOCAINE Case report of neurotoxicity when intravenous lidocaine is administered with procainamide. No significant interaction is expected when lidocaine is used for focal anaesthetic infiltration Likely to be an additive effect both may cause neurotoxicity in overdose Care should be taken when administering lidocaine as an infusion for patients taking procainamide... 

Transient and permanent nerve damage can occur after regional anesthesia, particularly neuraxial anesthesia. The mechanism of this nerve damage is unclear. Some studies have shown an indirect effect. However, in crayfish giant axon, lidocaine had a dose- and time-dependent effect on isolated nerve function in vitro (31). At high concentrations lidocaine caused irreversible conduction block and total loss of resting membrane potential. These results in an isolated nerve suggest a direct neurotoxic effect of lidocaine. 

The cauda has a tenuous blood supply, and in this patient with pre-existing vascular disease, perioperative hypotension and the use of intrathecal adrenaline may have precipitated ischemia in an area with very poor reserve. To follow this with an accidental large dose of lidocaine, which is neurotoxic in animals when directly applied and theorized to cause interruption of nerve blood supply, would add insult to injury. The authors questioned the wisdom of performing continuous epidural anesthesia in such patients, when frequent neurological assessments cannot be performed. 

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. 

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. 

Ropivacaine is an amide-type LA, a vasoconstrictor at less than 1% and a vasodilator at more than 1%. The fact that it is the pure S-enantiomer reduces its toxicity. Like phenol, it is metabolized by the liver and eliminated by the kidneys. When administered by dermal injection, it has a rapid onset of action (less than a minute) and the duration of action is longer than or equal to that of bupivacaine. Combining it with adrenaline does not prolong its duration of action, and a concentration of 0.75% provides longer anesthesia than a concentration of 1%. Neurological and cardiovascular tolerance to ropivacaine is much better than to bupivacaine. What is more, there is a considerable difference between the neurotoxic and cardiotoxic doses. The toxicity of ropivacaine is intermediate between that of lidocaine and bupivacaine. Direct intravascular injection of ropivacaine is still dangerous, however. 

A man with paroxysmal tachycardia, treated with oral procainamide 1 g every 5 hours and increasing doses of lidocaine by intravenous infusion (550 mg within 3.5 hours), became restless, noisy and delirious when given a further 250 mg intravenous dose of procainamide. The symptoms disappeared within 20 minutes of discontinuing the lidocaine. The reason is not understood but the symptoms suggest that the neurotoxic effects of the two drugs might be additive. Other studies in patients have shown that lidocaine plasma levels are unaffected by intravenous or oral procainamide. ... 

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