AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

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.

Pathophysiology

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

United States

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.

Mortality/Morbidity

If untreated, local anesthetic toxicity can result in seizures, respiratory depression or arrest, hypotension, cardiovascular collapse or cardiac arrest, and death.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

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:
• • Lightheadedness, dizziness
  • Visual disturbance
  • Headache
  • Perioral tingling, numbness or tingling of tongue
  • Sedation
  • Impaired concentration
  • Dysarthria
  • Tinnitus
  • Metallic taste
  • 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.

Causes

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Allergic reactions
Anaphylaxis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

Care should be guided by the clinical presentation. Although lidocaine blood levels correlate with toxicity, lidocaine blood levels should still be drawn.

Imaging Studies

Imaging studies are determined by the overall clinical picture (eg, consider a head CT scan in the case of a seizure when the etiology of the seizure is not apparent).

Procedures

• Obtain adequate intravenous access.
• Airway control may require intubation.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• If lidocaine toxicity is suspected, stop the injection immediately and prepare to treat the reaction.
• Ensure adequate oxygenation, whether by face mask or by intubation.
• Anticonvulsants such as benzodiazepines and barbiturates (diazepam 5-10 mg, thiopental 50-100 mg) are the drugs of choice for seizure control. Phenytoin is not effective and should be avoided. Succinylcholine is sometimes also used to terminate the neuromuscular effects of seizures. Because succinylcholine paralyzes all muscles, the patient requires intubation.
• • In severe reactions, monitor the cardiovascular system (CVS) and support the patient with intravenous fluids and vasopressors as required.
  • Metabolic acidosis may develop, and the use of sodium bicarbonate can be considered, although, as in other instances of acute metabolic acidosis, this is controversial.

Consultations

Consultation with an anesthesiologist can be helpful for difficult airway management. If intubation is not successful, cricothyroidotomy should be performed.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of therapy in CNS lidocaine toxicity are to secure a patent airway and to terminate the neuromuscular and cerebral manifestations of seizures.

Drug Category: Barbiturates

These agents terminate seizure effects.

Drug Category: Benzodiazepines

These agents terminate seizures. By binding to specific receptor site, these agents appear to potentiate effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Drug Category: Muscle relaxants

Facilitate airway control and terminate neuromuscular manifestations of seizures.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention:

• Know the toxic dose of the local anesthetic being used. Use the lowest concentration and volume of local anesthetic that still produces good results. Add epinephrine at a ratio of 1:200,000 to slow vascular uptake through vasoconstriction.
• Lidocaine
  • Without epinephrine, the maximum safe dose is approximately 3-5 (average 4) mg/kg. For example, a 70-kg adult should receive no more than 300 mg or 30 mL of a 1% solution.
  • With epinephrine, the maximum safe dose is approximately 7 mg/kg. For example, a 70-kg adult should receive no more than 500 mg or 50 mL of a 1% solution.
• Describe the early symptoms of local anesthetic overdose to patients and instruct them to inform the physician if they experience any of these effects. Be sure that patients understand the effects of local anesthetics and that they can communicate with the physician if symptoms occur.
• A careful injection method may help prevent toxic reactions. Perform high-volume (>5 mL) injections slowly, in 3-mL increments. Stop to aspirate after every 3 mL injected. Injecting local anesthetic in this manner reduces the chances of a large-volume intravascular injection.
• Maintain verbal contact with the patient during the procedure. This helps detect subtle symptoms, such as dysarthria, and more severe ones, such as changes in mental status.
• Because benzodiazepines raise the threshold for CNS symptoms but not for cardiovascular system (CVS) symptoms, heavy benzodiazepine premedication is likely to result in a patient progressing directly to CVS toxicity without showing preliminary signs of CNS toxicity.

Prognosis:

• If oxygenation, ventilation, and cardiac output are maintained, patients usually have a full recovery without sequelae. Otherwise, various hypoxic complications, or even death, are possible.

Patient Education:

• Inform patients that they had a reaction to an overdose of local anesthetic.
• Clarify the following points for the patient:
• • The reaction was not allergic in nature.
  • Patients do not have an increased risk for recurrence.
  • Patients do not have an increased risk for the development of seizures in the future.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to stop a large-volume local anesthetic injection every 3-5 mL to aspirate and check for early symptoms of a reaction
• Failure to investigate previous reactions to local anesthetics: The vast majority of reactions are toxicity-based, and allergic reactions are rare. However, if the patient has even a vague history of a reaction involving airway and cardiovascular problems, consider a potential allergic reaction.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Chang YY, Ho CM, Tsai SK. Cardiac arrest after intraurethral administration of lidocaine. J Formos Med Assoc. Aug 2005;104(8):605-6. [Medline].
2. Achar S, Kundu S. Principles of office anesthesia: part I. Infiltrative anesthesia. Am Fam Physician. Jul 1 2002;66(1):91-4. [Medline].
3. Carpenter RL, Mackey DC. Local Anesthetics. In: Barash PG, Cullen BF, Stoelting RK, eds. Clinical Anesthesia. Philadelphia, Pa: J.B. Lippencott; 1992;509-41.
4. Challapalli V, Tremont-Lukats IW, Mc Nicol. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev. CD003345.
5. Challapalli V, Tremont-Lukats IW, McNicol ED, et al. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev. 2005;CD003345.
6. Cox B, Durieux ME, Marcus MA. Toxicity of local anaesthetics. Best Pract Res Clin Anaesthesiol. Mar 2003;17(1):111-36. [Medline].
7. Dershwitz M, Hoke JF, Rosow CE, et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology. Apr 1996;84(4):812-20. [Medline].
8. Dorf E, Kuntz AF, Kelsey J, Holstege CP. Lidocaine-induced altered mental status and seizure after hematoma block. J Emerg Med. Oct 2006;31(3):251-3. [Medline].
9. Faccenda KA, Finucane BT. Complications of regional anaesthesia Incidence and prevention. Drug Saf. 2001;24(6):413-42. [Medline].
10. Isohanni MH, Ahonen J, Neuvonen PJ, Olkkola KT. Effect of ciprofloxin on the pharmacokinetics of intravenous lidocaine. Eur J Anaesthesiol. Oct 2005;22(10):795-9. [Medline].
11. Isohanni MH, Neuvonen PJ, Olkkola KT. Effect of fluvoxamine and erythromycin on the pharmacokinetics of oral lidocaine. Basic Clin Pharmacol Toxicol. Aug 2006;99(2):168-72. [Medline].
12. Toledo LS, Mauad R. Complications of body sculpture: prevention and treatment. Clin Plast Surg. Jan 2006;33(1):1-11, v. [Medline].
13. Miller RD. Local Anethesthetics. Miller's Anesthesia. 2006;6th edition:594-595.
14. Odaka Y, Takahashi T, Yamasaki A, et al. Prevention of halothane-induced hepatotoxicity by hemin pretreatment: protective role of heme oxygenase-1 induction. Biochem Pharmacol. Apr 1 2000;59(7):871-80. [Medline].
15. Paris PM, Yeale DM. Pain Management. Rosen's Emergency Medicine. 2006;6th:2913-2937.
16. Strichartz GR, Berde CB. Local Anesthetics. In: Miller RD, ed. Anesthesia. Philadelphia, Pa: Churchill Livingstone;. 1994;489-521.
17. Toledo LS, Mauad R. Complications of body sculpture: prevention and treatment. Clin Plast Surg. Jan 2006;33(1):1-11, v. [Medline].
18. Tremont-Lukats IW, Challapalli V, McNicol ED, Lau J, Carr DB. Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and meta-analysis. Anesth Analg. Dec 2005;101(6):1738-49. [Medline].
19. Tsui BC, Wagner A, Finucane B. Regional anaesthesia in the elderly: a clinical guide. Drugs Aging. 2004;21(14):895-910. [Medline].

Article Last Updated: May 30, 2008