Lidocaine - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Lidocaine is a short-acting local anesthetic of the amide type. At the heart of its mechanism of action is a decrease in the permeability of the membrane of a neuron for sodium ions. As a result, the rate of depolarization decreases and the excitation threshold increases, leading to reversible local numbness. Lidocaine are used to achieve conductive anesthesia in various parts of the body and control arrhythmias. It has a rapid onset of action (about one minute after intravenous administration and fifteen minutes after intramuscular injection), rapidly spreading to surrounding tissues.The action lasts 10-20 minutes and about 60-90 minutes after intravenous and intramuscular injection, respectively.

Pharmacokinetics:

Absorption

Systemic absorption of lidocaine is determined by the site of administration, the dose and its pharmacological profile. The maximum concentration in the blood is achieved after intercostal blockade, then (in decreasing order of concentration), after insertion into the lumbar epidural space, brachial plexus and subcutaneous tissues. The main factor determining the rate of absorption and concentration in the blood is the total administered dose, regardless of the site of administration. There is a linear relationship between the amount of lidocaine administered and the resulting maximum concentration of anesthetic in the blood.

Distribution

Lidocaine binds to plasma proteins, including a i acid glycoprotein (ACG) and albumin. The degree of binding is variable, amounting to approximately 66%. Plasma concentration of ACG in newborns is low, so they have a relatively high content of free biologically active fraction of lidocaine.

Lidocaine penetrates through blood-brain and placental barriers,

probably through passive diffusion.

Metabolism

Lidocaine is metabolized in the liver, about 90% of the administered dose is exposed N-dealkylation to form monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both contribute to the therapeutic and toxic effects of lidocaine. Pharmacological and toxic effects MEGX and GX comparable to those of lidocaine, but less pronounced. GX has a longer lidocaine, half-life (about 10 hours) and can be cumulated by repeated administration.

Metabolites, formed as a result of subsequent metabolism, are excreted in the urine, the content of unchanged lidocaine in the urine does not exceed 10%.

Excretion

The terminal period of lidocaine half-life after intravenous bolus administration to healthy adult volunteers is 1-2 hours. Terminal half-life GX is about 10 hours, MEGX - 2 hours.

Special patient groups

Due to rapid metabolism, the pharmacokinetics of lidocaine can be affected by conditions that interfere with liver function. In patients with hepatic dysfunction, the half-life of lidocaine may increase 2 or more times.

Impaired renal function does not affect the pharmacokinetics of lidocaine, but can lead to the cumulation of its metabolites.

In newborns there is a low concentration of ACG, so the connection with plasma proteins can be reduced. Due to the potentially high concentration of free fraction, the use of lidocaine in neonates is not recommended.

Indications:

Infiltration and regional types of anesthesia: conductive, epidural, intravenous regional anesthesia.

Contraindications:

- Pincreased sensitivity to any of the components of the drug;

- hypersensitivity to other amide local anesthetics in history;

- hypovolemic shock;

- infection of the site of the proposed injection;

- syndrome of weakness of the sinus node (especially in elderly patients);

- WPW syndrome (Wolff-Parkinson-White);

- acute decompensation of heart failure;

- atrioventricular (AV) blockade of II-III degree (except when an artificial pacemaker is installed);

- sinoauric blockade;

- violations of intraventricular conduction;

- cardiogenic shock.

It is also necessary to take into account the general contraindications to the conduct of this or that type of anesthesia:

- for anesthesia in obstetric practice - violations of intrauterine development of the fetus, fetoplacental insufficiency, prematurity, endurance, gestosis;

- for epidural anesthesia - severe hypotension, cardiogenic shock and hypovolemic shock, neurological diseases, septicemia, inability to perform a puncture due to deformity of the spine.

Carefully:Lidocaine should be administered with caution to patients with myasthenia gravis, epilepsy, chronic heart failure, bradycardia and respiratory depression, coagulopathy, AV disturbances and intraventricular conduction, convulsive disorders, Melkersson-Rosenthal syndrome, porphyria, and in the trimester of pregnancy (see section "Special instructions").

Pregnancy and lactation:Data on the effect of lidocaine on human fertility are not available. Lidocaine may be used during pregnancy and breastfeeding. It is necessary to adhere strictly to the prescribed dosage regimen.With complications or bleeding, epidural anesthesia with lidocaine in obstetrics is contraindicated. In some cases, paracervical blockade in pregnancy can lead to bradycardia or tachycardia in the fetus, which requires careful monitoring of heart rate in the fetus. Lidocaine in a small amount penetrates into breast milk. However, its oral bioavailability is very low, therefore, the amount of lidocaine that can occur with breast milk is insignificant, and therefore, the potential harm for the child is small. The doctor decides on the possibility of lidocaine during breastfeeding.

Dosing and Administration:

The dosage regimen should be selected based on the patient's reaction and place of administration. The drug should be administered at the lowest concentration and lowest dose, giving the desired effect. Lidocaine apply for infiltrative, conductive, intravenous regional, epidural and spinal anesthesia.

The volume of the solution to be administered depends on the type of anesthesia, the size of the anesthetic site, the nature and duration of the intervention.If there is a need to introduce a large volume with a low concentration, the standard solution is diluted with saline solution (0.9% sodium chloride solution). Dilution is carried out immediately before administration.

The maximum dose for adults is not more than 4.5 mg / kg, but not more than 300 mg; for intravenous regional anesthesia - no more than 4 mg / kg. Repeated administration within 24 hours is not recommended.

Doses recommended for adults

	10 mg / ml
Infiltration anesthesia: intracutaneously, subcutaneously, intramuscularly
Small interventions	2-10 ml (20-100 mg)
Large interventions	10-20 ml (100-200 mg)
Conduction Anesthesia (anesthesia / blockade of peripheral nerves, including with blockade of nerve plexuses)
Perineural:	3-20 ml (30-200 mg)
Blockade of the nerves of the fingers and toes	2-4 ml (20-10 mg)
Blockade of nerve plexuses	10-20 ml (100-200 mg)
Blockade of intercostal nerves	3 ml (30 mg)
Blockade of the brachial nerve	25-30 ml (250-300 mg)
Paravertebral anesthesia	3-5 ml (30-50 mg)
Vagosimpathetic blockade of the cervical	5 ml (50 mg)
Vagosimpathetic blockade: lumbar region	5-10 ml (50-100 mg)
Epidural anesthesia
Thoracic	20-30 ml (200-300 mg)
Lumbar	25-30 ml (250-300 mg)
The sacred (caudal)	20-30 ml (200-300 mg)
Intravenous regional anesthesia (the introduction of an anesthetic directly into the vein of the limb (provided that the tow is applied above the injection site))	Not more than 5 ml (50 mg)

It is not recommended to use continuous administration of anesthetic with a catheter; the maximum dose should not be repeated more than 90 minutes later.

Childhood

Recommended doses for children with neuromuscular blockade - up to 4.5 mg / kg solution, with intravenous regional anesthesia - 3 mg / kg solution. The maximum dose for children is 4.5 mg / kg, but not more than 100 mg.

Elderly and weakened patients

Elderly and weakened patients, the drug is administered in smaller doses corresponding to their age and physical state.

Co-administration with epinephrine

The effect of lidocaine can be prolonged by the addition of a 0.1% solution of epinephrine (0.1 ml per 20 ml of lidocaine). In this case, with regional anesthesia, the dose of lidocaine can be increased to 500 mg.

Side effects:

Undesirable reactions are described in accordance with the system-organ classes MedDRA.

Like other local anesthetics, unwanted reactions to lidocaine They are rare and, as a rule, due to increased plasma concentration due to accidental intravascular injection,excess dose or rapid absorption from areas with abundant blood supply, or afterhypersensitivity, idiosyncrasy, or reduced patient tolerance. Systemic toxicity reactions are mainly manifested by the central nervous and / or cardiovascular system (see also the "Overdose" section).

Immune system disorders

Hypersensitivity reactions (allergic or anaphylactoid reactions, anaphylactic shock) - see also disorders of the skin and subcutaneous tissues. Skin allergic test on lidocaine is considered unreliable.

Disorders from the nervous system and mental disorders

Neurological signs of systemic toxicity include dizziness, nervousness, tremor, paresthesia around the mouth, numbness of the tongue, drowsiness, convulsions, coma.

Reactions from the nervous system may be manifested by its excitation or inhibition. Symptoms of CNS stimulation may be short or do not occur at all, so the first manifestations of toxicity can serve as confusion and drowsiness, followed by coma and respiratory insufficiency.

Neurological complications of spinal anesthesia include transient neurologic symptoms, such as lower back pain, buttocks and legs. These symptoms develop, usually within 24 hours after anesthesia and are resolved within a few days. Following spinal anesthesia, lidocaine and similar agents describe individual cases of arachnoiditis and horse tail syndrome with persistent paresthesia, bowel and urinary tract dysfunction, or paralysis of the lower extremities. Most cases are due to the hyperbaric concentration of lidocaine or prolonged spinal infusion.

Disturbances on the part of the organ of sight

Signs of lidocaine toxicity can be blurred vision, diplopia and transient amaurosis, nystagmus.

A bilateral amaurosis may also be a consequence of an accidental introduction to the optic nerve bed during ophthalmic procedures. After retro and peribulbar anesthesia, inflammation of the eye and diplopia were reported (see section "Special instructions").

Violations from the organ of hearing and labyrinth

Noises in the ears, hyperaemia.

Disorders from the cardiovascular system

Cardiovascular reactions are manifested by arterial hypotension, bradycardia, myocardial depression (negative inotropic effect), arrhythmias, cardiac arrest or circulatory insufficiency.

Disturbances from the respiratory system, chest and mediastinal organs

Shortness of breath, bronchospasm, respiratory depression, respiratory arrest.

Disorders from the gastrointestinal tract

Nausea, vomiting.

Disturbances from the skin and subcutaneous tissues

Skin rashes, itching, hives, angioedema, edema of the face.

Overdose:

Symptoms: initial signs of intoxication - dizziness, nausea, vomiting, euphoria, drowsiness, headache, paresthesia, disorientation, impaired vision; then - convulsions of mimic muscles of the face with transition to tonic-clonic convulsions of skeletal muscles, psychomotor agitation, asthenia, apnea, bradycardia, lowering of arterial pressure, collapse, methemoglobinemia; when used in childbirth - in a newborn: bradycardia, oppression of the respiratory center, apnea.

Treatment: when the first signs of intoxication appear, the administration is stopped, the patient is transferred to a horizontal position and oxygenation is performed.When convulsions are administered intravenously 10 mg of diazepam, with bradycardia-m-holinoblokatory (atropine), with collapse - vasoconstrictors (norepinephrine, phenylephrine). If necessary, intubation, artificial ventilation, and other resuscitation measures are indicated. Hemodialysis is ineffective.

Interaction:

The toxicity of lidocaine increases with its simultaneous use with cimetidine and propranolol due to increased lidocaine concentrations, this requires a reduction in the dose of lidocaine. Both drugs reduce hepatic blood flow. Besides, cimetidine inhibits microsomal activity. Ranitidine slightly reduces the clearance of lidocaine, which leads to an increase in its concentration. An increase in serum lidocaine concentration can also cause antiviral agents (for example, amprenavir, atazanavir, darunavir, lopinavir).

Hypokalemia caused by diuretics can reduce the effect of lidocaine when they are used simultaneously (see section "Special instructions"), Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally similar to local anesthetics of the amide type (eg, antiarrhythmics, such as mexiletine, tokainid), since systemic toxic effects are additive. Separate studies of drug interactions between lidocaine and class III antiarrhythmics (eg, amiodarone) have not been conducted, but caution is advisable. In patients who are simultaneously receiving antipsychotic drugs, lengthening or lengthening the interval QT (for example, pimozide, sertindol, olanzapine, quetiapine, zotepin), prenylamine, epinephrine (with random intravenous administration) or antagonists of 5-HT₃-serotonin receptors (e.g., tropospheric, dolasetron), the risk of ventricular arrhythmias may increase.

The simultaneous use of quinupristin / dalfopristin can increase the concentration of lidocaine and thus increase the risk of ventricular arrhythmias; their simultaneous use should be avoided.

In patients simultaneously receiving muscle relaxants (eg, suxamethonium), the risk of an intensified and prolonged neuromuscular blockade may increase.

After using bupivacaine in patients who received verapamil and timolol, reported on the development of cardiovascular failure; lidocaine is close in structure to bupivacaine.

Dopamine and 5-hydroxytryptamine lower the threshold of convulsive readiness for lidocaine.

Opioids probably have a seizure effect, which is confirmed by the data that lidocaine reduces the convulsive threshold to fentanyl in humans.

The combination of opioids and antiemetics, sometimes used for sedation in children, can reduce the convulsive threshold to lidocaine and increase its inhibitory effect on the central nervous system.

The use of epinephrine along with lidocaine may reduce systemic absorption, but with occasional intravenous administration, the risk of ventricular tachycardia and ventricular fibrillation increases dramatically.

Simultaneous use of other antiarrhythmics, β-adrenoblockers and blockers of "slow" calcium channels can further reduce AV- carrying out, carrying out on ventricles and contractility. Simultaneous use of vasoconstrictor increases the duration of action of lidocaine.

Simultaneous use of lidocaine and ergot alkaloids (eg, ergotamine) can cause severe arterial hypotension. Caution should be exercised with prolonged use of antiepileptic drugs (phenytoin), barbiturates and other inhibitors of microsomal liver enzymes, as this can lead to a decrease in efficacy and, as a result, increased demand for lidocaine. On the other hand, intravenous administration of phenytoin can increase the inhibitory effect of lidocaine on the heart.

The analgesic effect of local anesthetics can be exacerbated by opioids and clonidine.

Ethyl alcohol, especially with prolonged abuse, can reduce the effect of local anesthetics.

Lidocaine is not compatible with amphotericin B, methohexiton and nitroglycerin. To mix lidocaine with other medicinal products is not recommended.

When treating the injection site of a local anesthetic with disinfectant solutions containing heavy metals, the risk of developing a local reaction in the form of increased soreness and edema increases. When using local anesthetic drugs for spinal anesthesia with guanadrel, guanethidine, mecamylamine, trimethofan kamzilato, the risk of severe arterial hypotension and bradycardia increases.

With the simultaneous use of lidocaine and hypnotics and sedatives, their oppressive effect on CNS.

When applied simultaneously with narcotic analgesics, an additive effect develops, which is used in epidural anesthesia, and the risk of respiratory depression increases. Simultaneous use of lidocaine with MAO inhibitors increases the risk of lowering blood pressure (furazolidone, procarbazine, selegiline).

Anticoagulants (including ardeparin sodium, dalteparin sodium, sodium danaparoid, sodium enoxaparin, heparin sodium, warfarin and others) increase the risk of bleeding.

Special instructions:

The introduction of lidocaine should be carried out by specialists with experience in carrying out and equipment for resuscitation. When introducing local anesthetics, it is necessary to have equipment for resuscitation.

It should be used with caution in patients with myasthenia gravis, epilepsy, chronic heart failure, bradycardia and respiratory depression, as well as in combination with drugs interacting with lidocaine and leading to increased bioavailability, potentiation of effects (eg, phenytoin) or lengthening ( for example, in hepatic or terminal renal failure, in which lidocaine metabolites can be accumulated).Patients receiving class III antiarrhythmic drugs (for example, amiodarone) it is necessary to establish close monitoring and ECG monitoring, since the influence on the heart can be potentiated. There were post-registration reports on chondrolisis in patients who had a long intra-articular infusion of local anesthetics after the operation. In most cases, chondrolisis was noted in the shoulder joint. Due to the many contributing factors and the inconsistency of the scientific literature on the mechanism for effecting the effect, a cause-and-effect relationship has not been identified. Prolonged intra-articular infusion is not an approved indication for the use of lidocaine. Intramuscular injection of lidocaine may increase the activity of creatine phosphokinase, which may make it difficult to diagnose acute myocardial infarction.

Shown, that lidocaine can cause porphyria in animals, its use in persons with porphyria should be avoided.

When administered to inflamed or infected tissues, the effect of lidocaine may be reduced.

Before the initiation of intravenous lidocaine, hypokalemia, hypoxia and acid-base disruption must be eliminated.

Some local anesthetic procedures can lead to serious adverse reactions, regardless of the local anesthetic used. Conducting anesthesia of the spinal nerves can lead to depression of the cardiovascular system, especially against the background of hypovolemia, therefore caution should be taken when conducting epidural anesthesia in patients with cardiovascular disorders. Epidural anesthesia can lead to arterial hypotension and bradycardia. The risk can be reduced by the preliminary administration of crystalloid or colloidal solutions. It is necessary to immediately stop arterial hypotension.

In some cases, paracervical blockade in pregnancy can lead to bradycardia or tachycardia in the fetus, which requires careful monitoring of heart rate in the fetus (see section "Use during pregnancy and during breastfeeding"). Introduction to the head and neck can lead to unintentional entry into the artery with the development of cerebral symptoms even in low doses.

Retrobulbaric administration in rare cases can lead to entry into the subarachnoid space of the skull,leading to severe / severe reactions, including cardiovascular failure, apnea, convulsions and temporary blindness.

Retro-and peribulbar injection of local anesthetics carries a low risk of persistent oculomotor dysfunction. The main reasons include trauma and (or) local toxic effect on muscles and (or) nerves. The severity of such reactions depends on the degree of injury, the concentration of the local anesthetic and the duration of its exposure in tissues. In this regard, any local anesthetic should be used in the lowest effective concentration and dose.

Solution for injection of lidocaine is not recommended for use in newborns. The optimal serum concentration of lidocaine, which avoids such toxicity as convulsions and arrhythmias, is not established in newborns.

Avoid intravascular injection, if not directly indicated.

Use with caution

- in patients with coagulopathy. Therapy with anticoagulants (eg, heparin), NSAIDs or plasma substitutes increases the tendency to bleeding. Accidental damage to blood vessels can lead to severe bleeding.If necessary, check bleeding time, activated partial thromboplastin time (APTT), and platelet count;

- patients with complete and incomplete blockade of intracardiac conduction, as local anesthetics can depress AV-holding;

- It is necessary to carefully monitor patients with convulsive disorders for symptomatology from the central nervous system. Low doses of lidocaine can also increase convulsive readiness. In patients with Melkersson-Rosenthal syndrome, allergic and toxic reactions from the nervous system in response to the introduction of local anesthetics can develop more often;

- third trimester of pregnancy.

Effect on the ability to drive transp. cf. and fur:After the introduction of local anesthetics, there may be a transient decrease in sensitivity and / or a motor block. Until these effects are resolved, patients are not advised to drive vehicles and work with mechanisms.

Form release / dosage:

Solution for injection 10 mg / ml.

Packaging:

5 ml per ampoule.

For 10 ampoules, together with a knife or scarifier for opening ampoules and instructions for medical use are placed in a box of cardboard with a corrugated liner.

5 ampoules are placed in a blister pack.2 blister packs together with a knife or scarifier for opening ampoules and instructions for medical use are placed in a pack of cardboard.

For 10 ampoules together with a knife or scarifier for opening ampoules and instructions for medical use are placed in a pack with a cardboard insert for fixing ampoules.

In the case of using ampoules with a kink ring or with a notch and a break point, the insertion of a knife or scarifier for opening ampoules is not provided.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002694

Date of registration:06.11.2014

Expiration Date:06.11.2019

The owner of the registration certificate:BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Manufacturer: & nbsp

BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Information update date: & nbsp28.02.2018

Illustrated instructions

Instructions

Lidocaine (Lidocain)