What Is Lidocaine Toxicity?

Lidocaine is a local anesthetic and antiarrhythmic drug. It is a derivative of cocaine, but it does not have the hallucinogenic and addictive ingredients. Lidocaine hydrochloride is a white crystalline powder, easily soluble in water, and has the same toxicity as procaine, but the local anesthetic effect is strong and durable, and it has good surface penetrating power. It can be injected or used as a surface. anesthesia. Lidocaine is a very good local anesthetic. It usually takes effect after one to three minutes, and the effect is maintained for one to three hours. Used to treat oral ulcers. It is not used very often as a heart rhythm disorder because of concerns about long-term side effects. A few people are allergic to lidocaine ^[1] . It was used in the treatment of arrhythmias in 1963. It is currently the drug for the prevention and treatment of acute myocardial infarction and various heart diseases with rapid ventricular arrhythmia. It is the first choice for ventricular premature beats, ventricular tachycardia and ventricular tremor in acute myocardial infarction.

Drug Name: Lidocaine
Alias: Sirocaine, Cyrocaine, Lidocaine Base, Lighocaine, Lignocaine
Foreign name: Lidocaine
Whether prescription drugs: prescription
Main indications: Acute myocardial infarction, surgery

Dosage form: Injections, capsules, etc.
Athletes use with caution: Use with caution
Melting point: 66-69
Boiling point: 350.8 at 760 mmHg
CAS number: 137-58-6
Flash point: 166

Lidocaine compounds

Chinese name: lidocaine

Chinese alias: N-diethylaminoacetyl-2,6-dimethylaniline; Lidocaine; N-diethylacetyl-2,6-dimethylaniline; 2-diethylamino-N -(2,6-dimethylphenyl) acetamide; sirocaine;

English name: lidocaine

English alias: L-Caine; Leostesin; 2-Diethylamino-N- (2,6-dimethylphenyl) acetamide; Esracaine; 2-diethylamino-2 ', 6'-acetoxylidide;

CAS number: 137-58-6

Molecular formula: C ₁₄ H ₂₂ N ₂ O

Molecular weight: 234.33700

Exact mass: 234.17300

PSA: 32.34000

LogP: 2.65670

Physical and chemical properties

Appearance and properties: white crystalline powder

Density: 1.026g / cm ³

Melting point: 66-69 ° C

Boiling point: 350.8ºC at 760mmHg

Flash point: 166ºC

Water solubility: almost insoluble

Lidocaine

Stability: stable. Incompatible with strong oxidants.

Storage conditions: Store in a cool, dry place. Keep container closed when not in use.

Vapor pressure: 4.28E-05mmHg at 25 ° C

Security Information

Packing level: III

Hazard category: 6.1 (b)

Customs Code: 2924299090

Dangerous Goods Transport Code: 3249

WGK Germany: 3

Danger category code: R22

Safety instructions: S22-S26-S36

RTECS number: AN7525000

Dangerous goods mark: Xn ^[1]

Specifications: 1. Aerosol: 25g (contains lidocaine 1.75g); 2. Injection: 0.2g (10ml), 0.4g (20ml) each.

production method

1. Chloroacetyl chloride method 2,6-dimethylaniline is chloroacetylated with chloroacetyl chloride, then condensed with diethylamine, and then acidified to form a salt to obtain lidocaine.

2. Methyl diethylaminoacetate method In the presence of sodium methoxide, 2,6-dimethylaniline is condensed with methyl N, N-diethylacetate, and then acidified to form a salt ^[1] .

use

This product is an amide local anesthetic. It is widely used in surface anesthesia, infiltration anesthesia, conductive anesthesia and epidural anesthesia ^[1] .

Lidocaine Drug Description

Lidocaine Pharmacology and Toxicology

This product is an amide local anesthetic. After blood absorption or intravenous administration, it has obvious excitement and inhibitory biphasic effect on the central nervous system, and there is no pioneer excitement. When the blood concentration is low, analgesia, lethargy, and pain threshold increase; as the dose increases Large, the effect or toxicity is enhanced, subcontaminated blood drug concentration has anticonvulsant effect; when the blood drug concentration exceeds 5mg · ml-1, convulsions can occur. At low doses, this product can promote K + outflow in myocardial cells and reduce myocardial autonomy, and has an anti-ventricular arrhythmia effect; at the therapeutic dose, it has no effect on the electrical activity of myocardial cells, atrioventricular conduction and myocardial contraction Significant effects; further increase in blood concentration can cause slower cardiac conduction velocity, atrioventricular block, inhibit myocardial contractility and reduce cardiac output.

Lidocaine Pharmacokinetics

Oral bioavailability is low, and the effect of the first pass through the liver is sharply reduced. Absorption is complete after intramuscular injection. After absorption, it is quickly distributed into the heart, brain, kidney and other blood-rich tissues, and then to fat and muscle tissue. Apparent volume of distribution is about 1L / kg, which decreases during heart failure. The protein binding rate is about 51%. The association rate is higher in smokers than in nonsmokers.

Effective after 5 to 15 minutes after intramuscular injection, the therapeutic concentration is reached 15 to 20 minutes after a single intramuscular injection of 200 mg for 60 to 90 minutes;

Effective immediately after intravenous injection (approximately 45 to 90 seconds) for 10 to 20 minutes. The blood concentration for treatment is 1.5 to 5 g / ml, and the blood concentration for poisoning is 5 g / ml or more. Continuous intravenous drip for 3-4 hours to reach steady-state blood drug concentration, 8 to 10 hours for patients with acute myocardial infarction. 90% is metabolized by the liver, and the metabolites monoethylglycylxylylamine (MEGX) and glycylxylylxylamine (GX) have pharmacological activity. For those who continue to instill intravenously for more than 24 hours, the metabolites can produce treatment and poisoning . The half-life after intravenous injection is about 10 minutes, and is about 1 to 2 hours. The GX half-life is about 10 hours longer, and the MEGX half-life is similar to that of the original drug. Patients with heart failure, liver disease, the elderly, and continuous intravenous drip for more than 24 to 36 hours, the clearance of this product slows down. Excreted by the kidney, 10% of the original drug, 58% of metabolites (GX), can not be removed by hemodialysis.

Lidocaine is more potent and prolonged than procaine, but it is also more toxic. The deethyl metabolite (monoethylglycinamide xylene) metabolized in the liver still has local anesthesia properties, increased toxicity, and is further degraded and excreted by the urine through amidase, and 10% of the amount is excreted in the original form.

Lidocaine clinical application

Applicable to acute ventricular arrhythmias caused by acute myocardial infarction, surgery, digitalis poisoning and cardiac catheterization, including ventricular premature beats, ventricular tachycardia and ventricular fibrillation. Secondly, it is also used in patients with persistent epilepsy with other anticonvulsants and local or spinal anesthesia. It can also relieve tinnitus.

Lidocaine usage dosage

Usual Adult:

Intramuscular injection, once at a weight of 4.3 mg / kg, can be repeated once in 60 to 90 minutes;

Intravenous injection, according to the weight of 1mg / kg (usually 50-100mg) as the first load of intravenous injection for 2 to 3 minutes, if necessary, repeat the injection 1 to 2 times every 5 minutes, the maximum amount within one hour does not exceed 300mg;

Intravenous infusion. After using the load, it can be maintained by intravenous infusion at a rate of 1 to 4 mg per minute; or intravenously at a rate of 0.015 to 0.03 mg / kg per minute.

The elderly, heart failure, cardiogenic shock, decreased liver blood flow, liver or kidney dysfunction should reduce the amount, 0.5 to 1 mg intravenously per minute.

Extreme: The maximum load within 1 hour of intramuscular or intravenous injection is 4.5mg / kg (or 300mg). The maximum maintenance amount is 4 mg per minute.

For lidocaine hydrochloride injection (1) 5ml: 100mg (2) 20ml: 400mg.

1.Common amount for adults

Sacral block is used for childbirth analgesia, the dosage is limited to 200mg (1.0%); for surgical analgesia can be increased to 200-250mg (1.0-1.5%).

epidural block, thoracolumbar, 250-300mg (1.5-2.0%).

Blocked infiltration of local anesthesia or intravenous injection, 50 200mg (0.25 0.5%).

Peripheral nerve block, brachial plexus (unilateral) 250-300mg (1.5%); dental, 20-100mg (2.0%); intercostal nerve (each), 30mg (1.0%); paracervical infiltration, left and right sides 100 mg (0.5 to 1.0%) each; paravertebral spinal nerve block (per branch), 20 to 50 mg (1.0%); Yin nerve, 100 mg (0.5 to 1.0%) on the left and right sides.

Sympathetic ganglion block, cervical stellate nerve 50mg (1.0%), waist 50-100mg (1.0%).

Limit once, generally do not exceed 200mg (4.0mg / kg), the amount of epinephrine in the medicinal solution can be increased to 200 ~ 250mg (6.0mg / kg). Intravenous block, 4 mg / kg. Intravenous injection of therapeutic drugs, the first initial dose of 1mg / kg, the extreme amount of 4mg / kg, adult intravenous drip is limited to 1mg per minute. Repeated dosing should be no less than 60 minutes.

2. The commonly used amount for children varies from individual to individual. The maximum total amount for one administration should not exceed 4.0 4.5mg / kg. 0.25 0.5% solution is usually used, and 1.0% solution is used in special cases.

Topical administration

Dosage form for external use, usage and dosage:

1. Ointment 5%, dental can be applied to the dry mucous membrane surface in the mouth; 2.5% ointment for external use on the skin to treat itching.

2. 2% gel glue. Adults often apply to the outer wall of the esophagus, throat, trachea, or urethra; for women, 5 to 7 ml of cotton swab can be applied to the vagina for local application; urethral dilatation or cystoscopy Up to 400mg. The 24-hour prescription is limited to 600mg.

3, mouthwash 2%, used for oral diseases, adults use 15ml each time, spit out once every 3 hours; for sore throat, can be swallowed when needed, the prescription is limited to 8 times in 24 hours, that is, 2.4g, reduce it for children.

Lidocaine 4. Topical solution 4%, generally applied or sprayed directly on the surface of the throat or oral mucosa before gastroscopy, and occasionally nasal stuffing. The prescription should not exceed 3.0mg / kg for 24 hours each time. Use with caution in children.

5. Aerosol or spray 2-4% can be used for endoscope, 10 ~ 30ml each time, prescription limit is 3.0mg / kg.

Block anesthesia, 1 ~ 2% solution, no more than 0.4g at a time; surface anesthesia, 1 ~ 2% solution, spray or dipped in medicine, once no more than 0.25g; infiltration anesthesia, 1 ~ 2% solution, no more than one hour Over 0.4g; for arrhythmia, intravenous injection of 1 3mg / kg, if it is not effective, reinject the same amount after 10 15 minutes. At the same time, take 100mg and add 5 10% glucose solution in 100 200ml for intravenous drip. The total amount of one treatment is 4-6mg / kg.

Lidocaine adverse reactions

The overall incidence is about 6.3%, and most adverse reactions are dose-related.

1. Nerve: Optic neuritis, dizziness, dizziness, nausea, vomiting, burnout, slurred speech, paresthesia and muscle tremors, convulsions, unconsciousness, and respiratory depression. Drug reduction or withdrawal is needed. In case of convulsions, diazepam, short-acting barbiturates or short-acting muscle relaxants can be given intravenously.

2. Cardiovascular: Large doses can produce severe sinus bradycardia, cardiac arrest, ventricular fibrillation, severe atrioventricular block, and decreased myocardial contractility. Timely discontinuation of medication is needed. Atropine and isoproterenol are used if necessary. Or pacemaker treatment; give oxygen, correct acidosis and booster drugs when blood pressure drops; maintain airway patency and other resuscitation measures; patients with atrial flutter may increase the ventricular rate when used.

3, allergic reactions: rash and edema should be discontinued, high blood concentration can cause cardiovascular depression and respiratory arrest. The occurrence of these adverse reactions is completely related to the accidental entry into the blood vessels. Skin tests have limited value in predicting allergic reactions.

4. Spinal injection or topical lidocaine can cause fatal bronchospasm. Adults may develop respiratory distress syndrome, but it is rare.

5. There have been reports of supraventricular tachycardia, torsional arrhythmia or hypotension.

Lidocaine Drug Interactions

1, -blockers can reduce liver blood flow, so it may reduce liver when combined

Lidocaine The elimination of the viscera caused an increase in adverse reactions.

Compound Lidocaine Ointment

2. The combination of neuromuscular blocking drugs with a larger dose of lidocaine (more than 5mg / kg by weight) can enhance the blocking effect of such drugs.

3. Combined with anticonvulsants, it can increase myocardial depression and cardiac arrest. In addition, the combination of the two, the central nervous system adverse reactions also increased. Phenytoin sodium and phenobarbital can also accelerate the liver metabolism of this product, thereby reducing the blood concentration after intravenous injection. It has been reported that intravenous injection of this product followed by intravenous injection of pentobarbital can cause asphyxiation to death.

4. When combined with other antiarrhythmic drugs such as quinidine, procainamide and propranolol, the efficacy and toxicity are increased. Combination with propranolol can cause sinoatrial arrest. Combined with procainamide, it can produce transient delirium and hallucinations, but does not affect the blood concentration of this product.

5. Isoproterenol, the test proves that the total clearance of this product will increase due to increased liver blood flow.

6. Norepinephrine. The test proves that the total clearance of this product is reduced because it reduces liver blood flow.

7. Combined with cimetidine and beta-blockers can reduce the clearance of this product and increase adverse reactions.

It has been reported that propranolol reduces lidocaine clearance and increases the incidence of adverse reactions. Lidocaine interacts well with beta receptor antagonists.

8. Used with succinyl chloride and other neuromuscular blockers to strengthen and prolong muscle relaxation.

Lidocaine contraindications

1. Cross-allergic reactions. Those who are allergic to other amine local anesthetics may also be allergic to this product, but there have been no reports of cross-allergic reactions between lidocaine, procainamine, and quinidine.

2. It has been reported that this product is injected intravenously before delivery, and the fetal blood concentration can reach 55-100% of the mother's blood concentration within a few minutes. There are also reports of fetal bradycardia or tachycardia after mother's medication, and even neonatal methemoglobinemia. Pregnant women should weigh the advantages and disadvantages of medication. Medication in neonates can cause poisoning. The T1 / 2 of preterm infants is 3.16 hours, which is longer than normal infants (1.8 hours).

Lidocaine 3. The dosage for the elderly should be adjusted according to the needs and tolerance level. Generally, the dosage for elderly patients (> 70 years) should be halved.

4. The following conditions should be disabled; Asthma syndrome; Severe cardiac block, including or degree atrioventricular block, double beam branch block; Sinus node dysfunction.

5. The following situations should be used with caution; congestive heart failure, severe myocardial damage; liver dysfunction; elderly; hypovolemia and shock; incomplete atrioventricular block or indoor block; decreased liver blood flow; renal dysfunction; severe plugged bradycardia; preexcitation syndrome (possibly exacerbated).

6. For patients suffering from heart and liver diseases, the dose of lidocaine should be reduced. The drug has a longer half-life in patients with liver disease. Because it can quickly pass through the placenta and has an extended half-life in the newborn, it can cause neonatal depression.

7, usually only in the original fetus with a slow heart rate will cause lethal bradycardia.

8, severe atrioventricular block is disabled.

Lidocaine precautions

1.Allergic to this product, congestive heart failure, severe myocardial damage, bradycardia, pre-excitation syndrome, patients with liver and kidney dysfunction, second- and third-degree atrioventricular block, history of major epilepsy, liver function Disable patients with severe insufficiency and shock.

2, pregnant women, nursing mothers with caution. Heart and liver dysfunction should be appropriately reduced.

3. Medications for newborns can easily cause poisoning. The half-life of preterm infants is about 3.6 hours, which is 1.8 hours longer than that of normal infants. The elderly should adjust the dosage according to the tolerance level and needs, and the dosage for patients older than 70 should be halved.

4. Intravenous injection limit is used for antiarrhythmia. For arteriosclerosis, vasospasm, anesthesia in diabetics and fingers (toes), vasoconstrictors (such as epinephrine hydrochloride) should not be added.

5. Blood pressure, electrocardiogram and serum electrolytes should be checked at any time during the medication. Blood concentration should be monitored during long-term use.

Other benefits of lidocaine

Lidocaine is a local anesthetic and can also be used for emergency treatment of ventricular arrhythmias. With the in-depth study of lidocaine, it has been found that it also shows better results in the treatment of other diseases. This will be summarized below.

1. Treatment of vestibular neuritis lidocaine can block the excitability of sympathetic nerves in blood vessels, reduce its contraction effect on vascular smooth muscle, and increase the excitability of parasympathetic nerves to achieve the purpose of improving blood microcirculation. It can improve blood supply to the blood vessels around the vestibular nerve of the inner ear and eliminate impediment to internal lymphatic reflux. Methods: 50 ~ 100 mg of lidocaine was given intravenously, and 200 ~ 400 mg of severe cases were added with 5% glucose intravenously once a day for 3 days as a course of treatment.

2. To prevent cardiovascular reactions during tracheal extubation. Intratracheal intubation in general anesthesia patients, at the end of the operation, the anesthetic dose needs to be reduced until the throat tracheal reflex recovers. During extubation, a cardiovascular reaction similar to that during intubation can occur, which can also cause cough, which is extremely unfavorable for patients with hypertension, coronary heart disease and high intracranial pressure. Lidocaine prevents this reaction by using an intravenous injection of lidocaine 1.5 mg / kg. Its mechanism is related to central inhibition or cardiac inhibition.

3. Treatment of severe neonatal convulsions For patients with recurrent seizures, the first load of lidocaine is 2 mg / kg, plus the initial maintenance amount of 6 mg / kg intravenously, which is gradually reduced within 3 days.

4. For gastroscopy intubation, 2% lidocaine is included in the mouth, swallow slowly for 5 minutes, and intubate for examination after 10 minutes. Compared with the 2% tetracaine spray method, lidocaine has the advantages of time saving, simplicity, and less pain, and lidocaine has a sedative effect, which can eliminate the patient's nervousness, reduce gastric secretion and gastric motility.

5. Treatment of Acute Gastric Abdominal Pain. Acute gastrointestinal abdominal pain is mostly caused by acute indigestion and increased gastric acid secretion, mucosal congestion and edema, and even spasm. Oral lidocaine can alleviate this pain, and the usage is 2% lidocaine 15 mg orally.

Lidocaine 6. For the treatment of epilepsy, lidocaine can pass through the blood-brain barrier, excitement and then inhibit the central neuron activity, and can block the transmission at the joint between the nerve and muscle. Intravenous injection with 0.1 g of lidocaine diluted, the onset was stopped, and relapse was still effective.

7, treatment of asthma lidocaine is a powerful inhibitor of irritating cough, can also inhibit bronchial asthma. Methods: 5 ml (100 mg) of lidocaine was nebulized and inhaled once a day. The breathing and heart rate returned to normal, the wheeze disappeared, and the arterial blood gas recovery time was significantly shorter than that of the control group.

8. Hiccup Lidocaine The mechanism of hiccup treatment may be related to its block effect on peripheral and central nerve conduction. Usage: 100 mg of lidocaine is added to a moffier dropper, and then 500 mg is added to 10% glucose to maintain a intravenous drip at a rate of 30 to 40 drops per minute. After hiccup control, it is maintained for 1 to 2 days.

9, treatment of renal colic lidocaine has antispasmodic, dilatation of the ureter and mild analgesic effect, can alleviate renal colic. After diluting with 100 mg of lidocaine, it was pushed statically, and then 200 mg was added to the intravenous infusion.

10. Non-inhibitory contraction of bladder after treatment. Lidocaine can penetrate the mucosa and block the conduction of peripheral nerves. It can be made into a gel for rectal administration, which can block the detrusor nerve conduction and inhibit the non-depressive detrusor shrink. Usage: It is rectally administered with verapamil 40 mg, and 5 minutes later, 2% lidocaine is reperfused in 20 ml, and the effective rate (71%) is higher than that of the verapamil group (38%).

Lidocaine anaphylactic shock

If the patient has the following symptoms after taking the medicine: (1) Respiratory symptoms caused by edema and spasms of the throat and bronchus: chest tightness, shortness of breath. Difficulty breathing. Asphyxia, cyanosis; (2) Symptoms of the circulatory system: pale, cold sweats, weak pulses, and decreased blood pressure; (3) loss of consciousness, incontinence, fainting, and coma, the occurrence of anaphylactic shock should be considered, lidocaine Once an allergic reaction occurs, the patient should immediately lie supine or slightly raise the torso of the head to facilitate breathing. Raising the lower limbs by 15 to 20 degrees is conducive to venous return, maintains breathing, and maintains a normal body temperature. It is necessary to fight against every second. For emergency rescue, you can immediately inject 1: 1000 epinephrine subcutaneously, once a dose, 0.5 to 1.0 ml for adults, 0.5 ml for children, intravenous injection if necessary. If the symptoms do not ease, continue subcutaneously or intravenously every 20 to 30 minutes. Inject 0.5ml until it is out of danger. If necessary, intramuscular intravenous dexamethasone, 2-20mg at a time, should pay attention to local rescue. Before the patient is not out of danger, it should not be transferred to the clinic or unnecessary movement. . At the same time as the above rescue, antihistamines and intravenous infusion of adrenal corticosteroids were applied. ^[2]

Lidocaine Expert Reviews

Lidocaine is a widely used intermediate-acting amide-type local anesthetic. Because of its higher fat solubility and protein binding rate than procaine and its ability to penetrate cells, lidocaine has a faster onset of action and a longer duration of action than procaine. It is 4 times stronger than procaine. Lidocaine has an effective rate of more than 80% for tachycardia caused by various causes, and it is safer. Therefore, lidocaine can be the drug of choice for acute ventricular arrhythmias caused by various causes.

Lidocaine poisoning

Lidocaine (Sirocaine) is an amide local anesthetic and antiarrhythmic.

The causes of poisoning are more common when the dosage is too large or the rate of intravenous injection is too fast. Patients with liver disease may have severe poisoning after long-term application of therapeutic doses. Patients with bradycardia or severe atrioventricular block may be worsened by applying this drug.

The drug is rapidly absorbed, and it takes effect 15-30 minutes after intravenous injection, and the duration of action is about 10-20 minutes. The drug effect occurred 5 minutes after intramuscular injection, and weakened after 45 to 60 minutes. Metabolites after oral administration are more toxic to the central nervous system.

90% of this product is metabolized by the liver, the ability of patients with liver dysfunction to remove lidocaine is reduced by 45%, the ability to clear this drug is reduced by 47% in heart failure, and only 10% -20% is excreted by the kidney.

The poisoning blood concentration of this medicine is 21.25 mol / L. If it reaches 25.5 mol / L, symptoms of central nervous system poisoning often occur.

This medicine mainly damages the nervous system, heart and produces allergic reactions.

Clinical manifestation

1. Central nervous system symptoms: drowsiness, dizziness, burnout, visual and hearing impairment, euphoria, restlessness, convulsions, paresthesia, nausea, vomiting, slurred speech, and difficulty breathing.

2. Extreme anxiety, insanity, disorientation, and psychiatric disorders, even epilepsy-like convulsions, decreased blood pressure, sinus bradycardia, atrioventricular block, and even sinus arrest, cardiac arrest and Breathing stopped.

3. Allergic reactions: rash, urticaria, bronchospasm, angioedema, and even anaphylactic shock.

treatment

The main points of treatment for lidocaine poisoning are:

1. Due to the rapid and short-term effects of this drug, the general adverse reactions and symptoms can often be resolved quickly after discontinuation.

2. After taking a large amount of this medicine by mistake, immediately inject 50% glucose solution to promote excretion.

3. Convulsions and convulsions with diazepam and barbiturates.

4. Blood pressure can be reduced with booster drugs.

5. Severe bradycardia, cardiac arrest, severe atrioventricular block, the drug should be discontinued in time and treated with atropine, isoprenaline or pacemaker installation.

6. Allergic reactions occur when given antihistamines or glucocorticoids ^[3] .