What is Lidocaine

Lidocaine is a commonly used local anesthetic (numbing medication) for pain control during minor surgery or invasive procedures such as biopsies, small excisions or dental work. Lidocaine works by blocking nerve signals in your body or blocking thenerve signals at the nerve endings in your skin. Lidocaine is chemically referred to as aminoethylamides or amide local anesthetic. Lidocaine is usually given as a single injection locally into a lesion or the area of incision, but can be given as infusions for hours or for several days by epidural or wound-based catheters. Lidocaine infusion can also be used for postoperative pain management. Lidocaine has an excellent tolerance and safety. Lidocaine injection is to be given only by or under the direct supervision of your doctor.

Local anesthetics have been shown to be effective and are used widely in preventing or reducing pain from minor surgery, incisions, biopsies, dental and obstetrical procedures and pain from wounds.

Lidocaine was approved for use as a local anesthetic in the 1948 originally under the commercial name Xylocaine, ropivacaine in 1990 (Naropin), and bupivacaine in 1990 (Marcaine). Other less commonly used amide anesthetics include articaine (Septocaine: 2000), mepivacaine (Carbocaine: 1960), and prilocaine (Citanest: 1965). A liposomal and longer acting preparation of bupivacaine was approved for use in controlling postsurgical pain in 2011 (Exparel). Side effects of the local anesthetics are usually dose related and occur mostly as a result of systemic administration or exposure. They include neurological symptoms such as drowsiness, tinnitus, dizziness and twitching as well as gastrointestinal effects such as nausea, vomiting and constipation. Cardiovascular depression can also occur and ventricular arrhythmias, especially with higher doses.

Lidocaine Patch

Lidocaine patches are used to relieve the pain of post-herpetic neuralgia, the burning, stabbing pains, or aches that may last for months or years after a shingles infection. Lidocaine patch is to be applied to the skin only once a day as needed for pain. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use lidocaine patches exactly as directed.

Your doctor will tell you how many lidocaine patches you may use at one time and the length of time you may wear the patches. Never apply more than three patches at one time, and never wear patches for more than 12 hours per day. Using too many patches or leaving patches on for too long may cause serious side effects.

To apply the lidocaine patches, follow these steps:

1. Look at the skin that you plan to cover with a lidocaine patch. If the skin is broken or blistered, do not apply a patch to that area.
2. Use scissors to remove the outer seal from the package. Then pull apart the zipper seal.
3. Remove up to three patches from the package and press the zipper seal tightly together. The remaining patches may dry out if the zipper seal is not tightly closed.
4. Cut patch(es) to the size and shape that will cover your most painful area.
5. Peel the transparent liner off the back of the patch(es).
6. Press the patch(es) firmly onto your skin. If you are applying a patch to your face, be careful not to let it touch your eyes. If you do get lidocaine in your eye, wash it with plenty of water or saline solution.
7. Wash your hands after handling lidocaine patches.
8. Do not reuse lidocaine patches. After you are finished using a patch, remove it and dispose of it out of reach of children and pets. Used patches contain enough medication to seriously harm a child or pet.

What is lidocaine used for?

Lidocaine is commonly used local anesthetic, often in combination with epinephrine, for pain control during minor surgery or invasive procedures such as biopsies, small excisions or dental work. Lidocaine injection is used to numb an area of your body to help reduce pain or discomfort caused by invasive medical procedures such as surgery, needle punctures, or insertion of a catheter or breathing tube. Lidocaine injection is sometimes used to treat irregular heart rhythms that may signal a possible heart attack. Lidocaine injection is also given in an epidural (spinal block) to reduce the discomfort of contractions during labor.

Lidocaine is usually given as a single injection locally into a lesion or the area of incision, but can be given as infusions for hours or for several days by epidural or wound-based catheters. Lidocaine infusion can also be used for postoperative pain management. Lidocaine has an excellent tolerance and safety. Lidocaine has variable duration of action, and short acting versions are often given with epinephrine, which acts as a vasopressor and extends its duration of action at a site by opposing the local vasodilatory effects of lidocaine, therefore decreases the rate of absorption limiting systemic exposure and prolonging the duration of action.

Infusions of lidocaine (and procaine) have been used to supplement general anesthetic techniques, as they are capable of reducing the minimum alveolar concentration of volatile anesthetics by up to 40% as well as providing pain relief in the peri-operative phase ¹. Given intravenously, lidocaine can be used during advanced airway management as an adjuvant to tracheal intubation, obtunding the hypertensive response to laryngoscopy and potentially reducing the incidence of myalgia and hyperkalemia when succinylcholine is given ². Lidocaine is a class Ib antiarrhythmic agent on the Vaughan-Williams classification, and its use is indicated in the management of acute ventricular tachydysrhythmias. It also has roles as an adjuvant analgesic in the management of chronic pain.

Lidocaine monitoring

Lidocaine local anesthetics are metabolized (N-dealkylation and hydroxylation) by microsomal P-450 enzymes in the liver ¹. Lidocaine has a narrow therapeutic index, and plasma level monitoring may be necessary for patients with hepatic impairment who are on prolonged infusions.

Lidocaine contraindications

Lidocaine is contraindicated in patients with a known severe adverse reaction. Anaphylactic reactions to lidocaine are possible but rare.

Methemoglobinemia can occur due to lidocaine metabolism to O-toluidine ³. This metabolite is more likely when very high doses are given, but it may also occur with lower doses where the patient is taking other medications that can precipitate methemoglobinemia, or where the patient has a hemoglobinopathy or another cause of anemia.

Lidocaine should not be used as an antiarrhythmic if the dysrhythmia may be secondary to local anesthetic toxicity.

Lidocaine preparations containing epinephrine cause demonstrable cardiovascular effects even if only given in small amounts, and it is prudent for basic hemodynamic monitoring to be carried out before and during use solutions containing vasopressors, particularly if there is any specific concern over the patient’s cardiovascular status ⁴.

How long does lidocaine last?

Lidocaine injection typically begins working within four minutes and lasts for half an hour and up to three hours.

Lidocaine mechanism of action

Lidocaine mechanism of anesthetic action is believed to be based upon inhibition of voltage-gated sodium ion channels on the internal surface of nerve cell membranes, which results in membrane stabilization and slowing of membrane depolarization and repolarization ². The uncharged form diffuses through neural sheaths into the axoplasm before it then ionizes by combining with hydrogen ions. The resulting cation binds reversibly to sodium channels from the inside, locking them in the open state and preventing nerve depolarization. As lidocaine is a weak base with a dissociation constant (pKa) of 7.7 ⁵, approximately 25% of molecules will be un-ionized at a physiological pH of 7.4 and will be available to translocate inside the nerve cells, meaning that lidocaine has a more rapid onset of action than other local anesthetics with higher pKa values. Efficacy decreases in the presence of inflammation; this can be due to acidosis decreasing the proportion of un-ionized lidocaine molecules, a faster decrease in lidocaine concentration due to increased blood flow, and potentially also increased production of inflammatory mediators like peroxynitrite which act directly on sodium channels ⁶.

In cardiac myocytes (heart muscle), lidocaine slows the rise of the cardiac action potential during phase 0, thereby increasing the effective threshold potential.

Lidocaine is 65% protein-bound to albumin and alpha1-acid glycoprotein in the plasma, giving it a medium duration of action compared to other local anesthetic agents. It is less lipid soluble than other agents, limiting its overall potency. Its volume of distribution is 0.7 to 1.5 L/kg and is hepatically metabolized.

Lidocaine special precautions

Before taking lidocaine:

You should not receive lidocaine if you are allergic to lidocaine injection or any other type of numbing medicine, or if you have:

• severe heart block;
• a heart rhythm disorder called Stokes-Adams syndrome (sudden slow heart beats that can cause you to faint); or
• a heart rhythm disorder called Wolff-Parkinson-White Syndrome (sudden fast heartbeats that can cause you to faint or become easily tired).

Tell your doctor if you have ever had:

• an allergy to corn products;
• liver disease;
• kidney disease;
• heart disease (unless you are being treated with lidocaine injection for a heart condition);
• coronary artery disease, circulation problems; or
• malignant hyperthermia.

Lidocaine may cause a rare, but serious blood problem called methemoglobinemia. The risk may be increased in children younger than 6 months of age, elderly patients, or patients with certain inborn defects. It is more likely to occur in patients receiving too much of the medicine, but can also occur with small amounts. Check with your doctor right away if you or your child has the following symptoms after receiving lidocaine: pale, gray, or blue-colored skin, lips, or nails, confusion, headache, lightheadedness, fast heartbeat, or unusual tiredness or weakness.

If you receive lidocaine into your lower back (epidural), you may experience temporary loss of sensation and movement, usually in the lower half of your body. Talk with your doctor if you have concerns.

It is not known whether lidocaine will harm an unborn baby. Tell your doctor if you are pregnant.

It may not be safe to breast-feed while using lidocaine. Ask your doctor about any risk.

Lidocaine may affect the results of certain medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

In deciding to use lidocaine, the risks of taking lidocaine must be weighed against the good it will do. This is a decision you and your doctor will make. For lidocaine, the following should be considered:

Lidocaine allergy

Tell your doctor if you have ever had any unusual or allergic reaction to lidocaine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Because of lidocaine’s toxicity, it should be used with extreme caution in children younger than 6 months of age. Recommended doses should not be exceeded, and the patient should be carefully monitored during treatment.

Geriatric

No information is available on the relationship of age to the effects of lidocaine injection in geriatric patients. However, because of lidocaine’s toxicity, it should be used with caution. Recommended doses should not be exceeded, and the patient should be carefully monitored during treatment.

Breastfeeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Lidocaine Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking lidocaine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using lidocaine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Dihydroergotamine
• Dronedarone
• Saquinavir
• Vernakalant

Using lidocaine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amifampridine
• Amiodarone
• Amprenavir
• Arbutamine
• Atazanavir
• Bupivacaine Liposome
• Bupropion
• Cobicistat
• Dasabuvir
• Delavirdine
• Disopyramide
• Donepezil
• Encainide
• Etravirine
• Flecainide
• Fosamprenavir
• Fosphenytoin
• Fospropofol
• Hyaluronidase
• Lacosamide
• Lopinavir
• Metoprolol
• Mexiletine
• Moricizine
• Nadolol
• Ombitasvir
• Paritaprevir
• Phenytoin
• Procainamide
• Propafenone
• Propofol
• Propranolol
• Quinidine
• Sotalol
• St John’s Wort
• Succinylcholine
• Telaprevir
• Tocainide

Using lidocaine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cimetidine
• Penbutolol

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of lidocaine. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood vessel disease or
• Heart disease or
• Hypertension (high blood pressure) or
• Liver disease—Use with caution. The chance of side effects may be increased.
• Brain or nerve disease or
• Heart block or
• Hypertension (high blood pressure), severe or
• Sepsis or
• Shock, severe or
• Spine problems—Use with caution.
• Glucose-6-phosphate dehydrogenase deficiency (G6PD) or
• Heart problems or
• Lung or breathing problems or
• Methemoglobinemia (blood disorder), hereditary or idiopathic (unknown cause)—Use with caution. May increase risk of having methemoglobinemia.

Lidocaine can impair the ability of iron in red blood cells to carry oxygen to the tissues. Methemoglobinemia is the condition of having blood that has this altered kind of iron. Methemoglobinemia can result even from normal use of lidocaine, especially in children. Because the blood is not able to carry enough oxygen to the tissues, people with methemoglobinemia appear very pale or even blue, feel very tired, and have shortness of breath. Methemoglobinemia can be life-threatening.

How is lidocaine injection given?

A nurse or other trained health professional will give you lidocaine in a medical facility. It is given through a needle placed into one of your veins, into your upper arm, into the head and neck area, or into the space around the spinal nerves in your lower back.

Lidocaine may cause significant pain on initial injection due to the agent stimulating nociceptors before it exerts its effects on sodium channels; this can be counteracted by buffering the lidocaine with small volumes of sodium bicarbonate shortly before use, making the solution less acidic ⁷. Pain can also be reduced by warming the solution to body temperature, injecting more slowly, using narrow cannulas, and injecting at 90 degrees to the skin ⁸.

When used to treat heart rhythm problems, lidocaine is given as an infusion into a vein.

When used as a local anesthetic, lidocaine is injected through the skin directly into the body area to be numbed.

Your breathing, blood pressure, oxygen levels, and other vital signs will be watched closely while you are receiving lidocaine injection in a hospital setting.

If you are being treated for irregular heart rhythm, your heart rate will be constantly monitored using an electrocardiograph or ECG (sometimes called an EKG). This will help your doctor determine how long to treat you with lidocaine injection.

Lidocaine side effects

Along with lidocaine’s needed effects, lidocaine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Lidocaine injection can cause side effects that may impair your thinking or reactions. Unless absolutely necessary, do not drive after receiving lidocaine injection.

Avoid eating or chewing within 1 hour after lidocaine injection is used to numb your mouth or throat. You may have trouble swallowing which could lead to choking. You may also accidentally bite the inside of your mouth if you are still numb an hour after treatment with lidocaine injection.

Most lidocaine side effects occur when lidocaine’s plasma concentrations rise to toxic levels. Lidocaine reaches the intravascular compartment most rapidly when it is administered into the intercostal space, followed by the caudal, epidural, brachial plexus, femoral and subcutaneous spaces. The maximum safe dose by body weight may be taken to be 3 mg/kg, or 7 mg/kg when using preparations with epinephrine, although the literature quotes various other doses ². Smaller amounts than this can still result in side effects and toxicity if given intravascularly.

Lidocaine is thought to be more neurotoxic than other local anesthetics, especially when high concentrations applied directly to nervous tissue. Use of highly concentrated lidocaine (2.5 to 5%) for spinal anesthesia correlates with a greater incidence of transient radicular irritation syndrome, which is a self-limiting painful condition affecting the calves, thighs, and buttocks ⁷.

Check with your doctor or nurse immediately if any of the following side effects occur:

Incidence not known:

• bluish-colored lips, fingernails, or palms blurred or double vision
• chest pain or discomfort
• cold, clammy, pale skin
• confusion
• continuing ringing or buzzing or other unexplained noise in the ears
• cough
• dark urine
• difficulty breathing
• difficulty swallowing
• dizziness or lightheadedness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• fast heartbeat
• fever
• headache
• hearing loss
• hives, itching, skin rash
• irregular heartbeat
• irregular, fast or slow, or shallow breathing
• loss of consciousness
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid or slow heart rate
• seizures
• slow or irregular heartbeat
• sore throat
• sweating
• tightness in the chest
• tremor
• twitching
• unusual bleeding or bruising
• unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

• cold or numb feeling
• false or unusual sense of well-being
• feeling of heat
• loss of bladder and bowel control
• loss of genital sensation and sexual function
• nervousness
• vomiting

Other lidocaine side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Lidocaine patch side effects

Lidocaine patches may cause side effects. If any of these symptoms occur, remove your patch and do not put it back on until the symptoms go away. Tell your doctor if any of these symptoms are severe or do not go away:

• burning or discomfort in the place you applied the patch
• redness or swelling of the skin under the patch

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor immediately:

• hives
• skin rash
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• cool, moist skin
• fast pulse or breathing
• unusual thirst
• nausea
• vomiting
• confusion
• weakness
• dizziness
• fainting

Lidocaine patches may cause other side effects. Call your doctor if you have any unusual problems while using lidocaine patches.

Lidocaine toxicity

Applied either by injection, inhalation, or as a topical agent to provide anesthesia, lidocaine has a good safety margin before reaching toxic blood levels.  Lidocaine toxicity not only is determined by the total dose (usually 4.5 mg/kg) but also by the rate of absorption, which is dependent on the blood flow of that tissue. To reduce blood flow to the injection site and therefore the rate of absorption, vasoconstrictors such as epinephrine 1:200,000 is frequently used and may increase the toxic dose to 7 mg/kg ⁹. Patients who are likely to be more susceptible to local anesthetic toxicity are patients at the extremes of age and women who are pregnant. Rates of severe systemic toxicity (seizures with or without cardiac arrest) occur on the order of 1:10,000 for epidurals and up to 1:2000 for peripheral nerve blocks, depending on the type of block ¹.

Lidocaine toxicity to muscles and peripheral or neuraxial nerves can occur locally at the site of injection. Transient neurologic symptoms after high concentration lidocaine spinal anesthetics have been described multiple times and have led to either reducing the concentration of the dose or switching to a different agent.

In addition to direct nerve toxicity, systemic toxicity affecting the brain and/or cardiac muscle can lead to sudden and dramatic changes in the patient’s vital signs.

Finally, there are the side effects of a relative overdose at the site of injection, which can be quite dramatic. Examples include total spinal anesthesia or subdural injection of the drug that can cause severe hemodynamic compromise such as hypotension or bradycardia up to a cardiac and respiratory arrest.

Lidocaine toxicity to local nerves and muscles are thought to be a consequence of the prolonged application of high drug concentrations or the effect of preservatives in the local anesthetic solution or both ¹⁰.

Systemic local anesthetic toxicity is due to high systemic plasma levels of lidocaine due to absorption of large doses of lidocaine, which depends mostly on the blood flow at the site of injection: tracheal > intercostal > caudal > paracervical > epidural > brachial plexus > subcutaneous.

Also, blind injection of large volumes into a large muscular area, such as for lumbar plexus block or sciatic nerve blocks, have all of the elements that could lead to systemic lidocaine toxicity.

Spinal anesthetics are very low in total dose and would not cause systemic lidocaine toxicity.

Inadvertent intra-arterial injections may cause local anesthetic toxicity in the tissue beds supplied by that artery even well under the systemic toxic concentration. This complication is seen mostly with injections into the neck, causing central nervous system (CNS) symptoms often during the injection or shortly after that without progressing to the feared cardiac toxicity.

Signs and symptoms of mild lidocaine toxicity become apparent at plasma levels greater than 5 mcg/mL, beginning with slurred speech, tinnitus, circumoral paresthesiae and feeling faint ². Above 10 mcg/mL, the patient may experience seizures or loss of consciousness. The myocardium and central nervous system are further depressed at 15 mcg/mL, progressing to cardiac arrhythmias, respiratory arrest and cardiac arrest above 20 mcg/mL ¹¹. Animal studies suggest that the dose of lidocaine required to result in cardiovascular collapse is 7.1 times higher than the dose needed to induce seizures ¹². This ratio is significantly higher than other local anesthetic agents, meaning that lidocaine may be less likely than other local anesthetics to progress rapidly through neurological signs and symptoms to full cardiovascular collapse in cases of toxic dosing.

Administration of the drug should immediately cease if toxicity is suspected. In the case of cardiorespiratory collapse, there should be airway support and breathing assistance to prevent the development of respiratory acidosis, which may exacerbate toxicity and potentiate lidocaine’s negative chronotropic and inotropic effects ¹³. Vital function support including oxygen, IV fluids, and inotropes should be instituted if required. Intravenous lipid emulsion is indicated as a rescue therapy, especially in cases of refractory cardiovascular collapse ¹².

Lidocaine toxicity treatment

Treatment of lidocaine toxicity is symptomatic by raising the seizure threshold through pharmacologic interventions such as administering benzodiazepines and/or barbiturates or propofol. Hyperventilation with high doses of oxygen reduces cerebral blood flow and also has been used to raise the seizure threshold ¹⁴.

The other mainstay of treatment is to reduce the free available lidocaine concentration in the plasma by administration of lipid emulsions. Due to the high lipid solubility, infusion of lipid emulsions will bind free circulating lidocaine and lower the plasma levels. The following is the treatment algorithm suggested by the American Society of Regional Anesthesia and Pain Medicine:

“Call for Help”

• Even premonitory CNS (central nervous system) systems may progress to severe cardio-respiratory compromise, and many tasks may need to be done simultaneously such as getting code carts and fetching the lipid emulsion.

Initial Focus

• Airway management: ventilate with 100% oxygen
• Seizure suppression: benzodiazepines are preferred; AVOID propofol in patients having signs of cardiovascular instability

Alert the Nearest Facility Having Cardiopulmonary Bypass Capability

Management of Cardiac Arrhythmias

• Basic and Advanced Cardiac Life Support (ACLS) will require adjustment of medications and perhaps prolonged effort
• AVOID vasopressin, calcium channel blockers, beta-blockers, or local anesthetic
• REDUCE individual epinephrine doses to <1 mcg/kg

Lipid Emulsion (20%) Therapy (values in parenthesis are for 70kg patient)

• Bolus 1.5 mL/kg (lean body mass) intravenously over 1 minute (~100mL)
• Continuous infusion 0.25 mL/kg/min (~18 mL/min; adjust by roller clamp)
• Repeat bolus once or twice for persistent cardiovascular collapse
• Double the infusion rate to 0.5 mL/kg/min if blood pressure remains low
• Continue infusion for at least 10 minutes after attaining circulatory stability
• Recommended upper limit: Approximately ten mL/kg lipid emulsion over the first 30 minutes”

Resuscitation during lidocaine toxicity may need to include cardiopulmonary bypass, as successful outcomes have been reported even after prolonged resuscitation, which may, in part, be explained by suggestions in animal models that bupivacaine, when added to cardioplegia solution, actually improves function and reduces the cellular damage of rat isolated hearts after prolonged, cold storage.

Lidocaine toxicity prognosis

The prognosis of lidocaine toxicity depends on the site of manifestation. CNS toxicity is either self-limited or quite amenable to treatment with benzodiazepines, has a good prognosis without complications and does not need further neurologic testing. Cardiac toxicity may require prolonged resuscitation, but the prognosis after return to spontaneous circulation is often very good ¹.

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