Lidocaine is an amide local anesthetic and a less commonly used antiarrhythmic that exerts its effects on nerve axon sodium channels, preventing depolarization.
Lidocaine toxicity occurs with unintended intravascular administration or with administration of an excessive dose. When lidocaine is used for regional nerve blocks, plasma levels are usually 3-5 mcg/mL. Toxicities may be observed at 6 mcg/mL, but more commonly occur once levels exceed 10 mcg/mL.
In addition to the dose administered, several factors modulate the degree of toxicity, including the relative vascularity of the injection site and the speed of the injection. Because lidocaine is hepatically metabolized, liver dysfunction increases the risk of toxicity. Because lidocaine is also protein bound, low protein states may also increase risk. Acidosis increases the risk because this setting favors lidocaine dissociation from plasma proteins.
Medication interactions also affect lidocaine drug levels. Some common medications that may interact include: cimetidine, ciprofloxacin, clonidine, phenytoin, and beta-blockers such as propranolol, metoprolol, and nadolol.
Lidocaine’s main effects are due to decreased conductance of sodium channels, antiarrhythmic effect, sedation, and neural blockade.
Lidocaine is hepatically metabolized and renally excreted, with only 10% unmodified.
CNS lidocaine toxicity is biphasic. The earlier manifestations are due to CNS excitation, with problems such as seizures. Subsequent manifestations include CNS depression with a cessation of convulsions and the onset of unconsciousness and respiratory depression or arrest. This biphasic effect occurs because local anesthetics first block inhibitory CNS pathways (resulting in stimulation) and then eventually block both inhibitory and excitatory pathways (resulting in overall CNS inhibition).
Higher serum concentrations of local anesthetics cause cardiovascular effects. Local anesthetics block sodium channels through a fast-in, slow-out mechanism that affects impulse conduction through the heart and nerve tissue. In the heart, this mechanism depresses Vmax (ie, the rate of depolarization during phase 0 of the cardiac action potential) and may lead to reentrant arrhythmias. Additionally, conduction through the sinus and atrioventricular nodes is suppressed. Acceleration of the ventricular rate has been reported in patients with atrial arrhythmias. Lidocaine also may elevate fibrillation thresholds.
Frequency is difficult to determine because lidocaine and other local anesthetics are used widely in a variety of settings, and most reactions are not reported.
One study estimated that when lidocaine is used in regional anesthesia, local anesthetic toxicity has a prevalence rate of 0.2% after epidural anesthesia and 1.45% following brachial plexus block.
If untreated, local anesthetic toxicity can result in seizures, respiratory depression or arrest, hypotension, cardiovascular collapse or cardiac arrest, and death.
The symptoms of lidocaine toxicity tend to follow a predictable progression. The toxicity begins with numbness of the tongue, lightheadedness, and visual disturbances and progresses to muscle twitching, unconsciousness, and seizures, then coma, respiratory arrest, and cardiovascular depression.
CNS toxicity: When the lidocaine dose is increased from 1 mg/kg to 1.5 mg/kg, the risk of CNS toxicity increases from 10% to 80%. Symptoms include the following:
Perioral tingling, numbness or tingling of tongue
Muscular twitching, tremors
With progression of toxicity, the patient may experience tonic-clonic seizures and, eventually, unconsciousness and coma. Seizures generally do not occur with lidocaine levels of less than 10 mcg/mL.
Cardiovascular: Excessive lidocaine concentration can cause cardiovascular toxicity, although this is less common than CNS toxicity. Lidocaine is somewhat less cardiotoxic than lipophilic local anesthetics such as bupivacaine. Risk of cardiac toxicity is greatest in those patients with underlying cardiac conduction problems or after myocardial infarction. Potential cardiovascular effects include the following:
Negative inotropic effects
Effects on vascular tone (with low doses having vasoconstrictive effects and higher doses causing relaxation of vascular smooth muscle)
Effects on cardiac conduction (including widened PR interval, widened QRS duration, sinus tachycardia, sinus arrest, and partial or complete atrioventricular dissociation. Cardiac arrest has been reported after intraurethral administration of lidocaine.1)
Cardiac toxicity is potentiated by acidosis, hypercapnia, and hypoxia, which worsen cardiac suppression and increase the chance of arrhythmia. This is important to consider since seizure makes this metabolic picture more likely.
Plasma lidocaine levels of less than 5 mcg/mL are unlikely to have cardiovascular toxicities. Levels of 5-10 mcg/mL can cause hypotension by inducing both cardiac suppression and vascular smooth muscle relaxation. Levels of more than 30 mcg/mL are associated with cardiovascular collapse.
Lidocaine should be avoided in persons with Wolff-Parkinson-White syndrome.
CNS symptoms may be masked in patients premedicated with anticonvulsants such as benzodiazepines or barbiturates. The first sign of toxicity in these premedicated patients may be cardiovascular system (CVS) depression.
When blood levels are high enough to block inhibitory and excitatory pathways, convulsions cease and the patient experiences respiratory depression or arrest and cardiovascular depression.
Large bolus injections may increase peak anesthetic levels to the point where the CNS and CVS are simultaneously affected.
The most common cause of lidocaine toxicity is dosing error.
The maximum recommended dose of lidocaine without epinephrine is 3-5 mg/kg; if given with epinephrine, up to 7 mg/kg may be given. Note that dosing may require modification based on patient characteristics and site of administration.
Although lidocaine toxicity is ultimately a simple matter of excessive blood concentration, several factors can influence the development of these reactions. Influential factors include the speed of the injection, the dose of the local anesthetic injected, acid-base status, hypercapnia, hypoxia, plasma protein level, and hepatic function.
Concurrent administration of other drugs, such as benzodiazepines, may mask the development of CNS symptoms but not CVS symptoms.
Lidocaine crosses the placenta.