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

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

Lidocaine is rapidly absorbed from the gastrointestinal tract, but due to the effect of the "primary passage" through the liver, only a small amount of it reaches the systemic blood flow.

Systemic absorption of lidocaine is determined by the site of administration and dose. 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 α₁acid glycoprotein (ACG) and albumin. The degree of binding is variable, about 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 the 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:

Local and regional anesthesia, conductive anesthesia for large and small surgical interventions.

Contraindications:

Hypersensitivity to the components of the drug and to anesthetics of the amide type; atrioventricular (AV) blockade of the third degree; hypovolemia.

Carefully:

The administration of lidocaine should be performed with caution in patients with myasthenia gravis gravis, epilepsy, chronic heart failure, bradycardia and respiratory depression, coagulopathy, complete and incomplete blockade of intracardiac conduction, convulsive disorders, Melkersson-Rosenthal syndrome, porphyria, and in the third trimester of pregnancy (see section "Special instructions").

Pregnancy and lactation:

Fertility

Data on the effect of lidocaine on human fertility are not available.

Pregnancy

Lidocaine may be used during pregnancy and breastfeeding. It is necessary to adhere strictly to the prescribed dosage regimen. With complications or bleeding in an anamnesis, epidural anesthesia with lidocaine in obstetrics is contraindicated.

Lidocaine was used in a large number of pregnant women and women of childbearing age. Any reproductive disorders are not registered, i.e. an increase in the frequency of malformations was not noted.

Due to the potential achievement of a high concentration of local anesthetics in the fetus after paracervical blockade, it may develop unwanted reactions, such as fetal bradycardia. Concerning lidocaine in a concentration exceeding 1%, in obstetrics do not apply.

In animal studies, no harmful effects on the fetus were detected.

Breast-feeding

Lidocaine in a small amount penetrates into breast milk, its oral bioavailability is very low. Thus, the expected amount coming with breast milk is very small, therefore, the potential harm for the child is very low.The doctor decides whether to use 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. The maximum dose for adults should not exceed 300 mg.

The volume of solution to be administered depends on the size of the anesthetized area. 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). Breeding is carried out immediately before the introduction.

Children, elderly and weakened patients drug are administered in smaller doses corresponding to their age and physical state.

In adults and children 12-18 years a single dose of lidocaine (with the exception of spinal anesthesia) should not exceed 5 mg / kg, with a maximum dose of 300 mg.

Doses recommended for adults

	10 mg / ml	20 mg / ml
Infiltration anesthesia:
Small interventions	2-10 ml (20-100 mg)
Large interventions	10-20 ml (100-200 mg)	5-10 ml (100-200 mg)
Conduction Anesthesia	3-20 ml (30-200 mg)	1.5-10 ml (30-200 mg)
Anesthesia of the fingers / toes	2-4 ml (20-40 mg)	2-4 ml (40-80 mg)
Epidural, lumbar	25-30 ml (250-300 mg)
Caudal, thoracic blockade	20-30 ml (200-300 mg)
Regional anesthesia	Not more than 5 ml (50 mg)	Not more than 2.5 ml (50 mg)

Children under 1 year old

Experience in children younger than 1 year is limited. The maximum dose in children 1-12 years is 5 mg / kg body weight 1% solution.

Co-administration with epinephrine

To lengthen the action of lidocaine and reduce its systemic action, it is possible to add ex tempore 0.1% solution of epinephrine in the ratio from 1: 100000 to 1: 200000.

Side effects:

Undesirable reactions are described in accordance with the system-organ classes MedDRA. The frequency is defined as follows:

Like other local anesthetics, unwanted reactions to lidocaine are rare and are usually caused by an increased plasma concentration due to accidental intravascular administration, exceeding the dose or rapid absorption from areas with abundant blood supply, or due to hypersensitivity, 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 signs of CNS depression - 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. After spinal anesthesia with lidocaine and similar means, individual cases of arachnoiditis and horse tail syndrome with paresthesia are described,dysfunction of the intestine and urinary tract 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.

Bilateral amaurosis can also be a consequence of accidental insertion into 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 of the cardiovascular system

Cardiovascular reactions are manifested by arterial hypotension, bradycardia, oppression of the contractile function of the myocardium (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

Rash, hives, angioedema, edema of the face.

Overdose:

Symptoms

Toxicity from the central nervous system is manifested by symptoms, increasing in severity. First, paresthesia around the mouth, numbness of the tongue, dizziness, hyperacusis and tinnitus can develop. Visual impairment and muscle tremor or muscle twitching indicate more serious toxicity and precedes generalized seizures. Then, loss of consciousness and large seizures can occur from a few seconds to several minutes. Seizures lead to a rapid increase in hypoxia and hypercapnia due to increased muscle activity and respiratory failure. In severe cases, apnea may develop. Acidosis increases the toxic effects of local anesthetics.

In severe cases, there are violations of the cardiovascular system. At a high systemic concentration, hypotension, bradycardia, arrhythmia and cardiac arrest may develop, which can be fatal.

The overdose solution is due to the redistribution of the local anesthetic from the central nervous system and its metabolism, it can proceed quickly enough (unless a very large dose of the drug has been administered).

Treatment

If there are signs of an overdose, the injection of the anesthetic should be stopped immediately.

Convulsions, CNS depression and cardiotoxicity require medical intervention. The main goals of therapy are to maintain oxygenation, stop convulsions, maintain adequate blood circulation and stop acidosis (if it develops). Where appropriate, it is necessary to ensure airway patency and designate oxygen, and also to establish auxiliary ventilation of the lungs (masochnuyu or using an Ambu bag). Maintenance of blood circulation is carried out by infusion of plasma or infusion solutions. If prolonged maintenance of blood circulation is necessary, the possibility of introducing vasopressors should be considered, but they increase the risk of CNS excitation. Control of seizures can be achieved by intravenous diazepam (0.1 mg / kg) or thiopental sodium (1-3mg / kg), while it should be borne in mind that anticonvulsants can also depress respiration and circulation. Prolonged convulsions can interfere with lung ventilation and oxygenation of the patient, and therefore the possibility of early endotracheal intubation should be considered. When the heart is stopped, they start a standard cardiopulmonary resuscitation.

The effectiveness of dialysis in the treatment of acute overdose with lidocaine is very low.

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 (e.g., pimozide, sertindole, 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 who simultaneously receive muscle relaxants (for example, suxamethonium),may increase the risk of an intensified and prolonged neuromuscular blockade.

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, βadrenoblockers 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 when using sedatives, as they may affect the action of local anesthetics on the CNS.

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.

With the simultaneous use of lidocaine with narcotic analgesics, an additive effect develops, which is used in epidural anesthesia, but it increases the inhibition of the central nervous system and respiration.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) lengthen the local anesthetic effect of lidocaine and can cause an increase in blood pressure and tachycardia.

Use with monoamine oxidase inhibitors (furazolidone, procarbazine, seleginin) probably enhances the local anesthetic effect of lidocaine and increases the risk of lowering blood pressure.

Guanadrel, guanethidine, mecamylamine, trimetaphane camsylate increase the risk of pronounced reduction in blood pressure and bradycardia.

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

Lidocaine reduces the cardiotonic effect of digitoxin.

Lidocaine reduces the effect of antimiasthenic drugs, enhances and lengthens the action of myorelaxing drugs.

When treating the injection site with disinfectant solutions containing heavy metals, the risk of developing a local reaction in the form of tenderness and swelling increases.

To mix lidocaine with other medicinal products is not recommended.

Special instructions:

Regional and local anesthesia should be carried out by experienced specialists in an appropriately equipped room with availability of ready-to-use equipment and preparations necessary for cardiac monitoring and resuscitation. Personnel performing anesthesia should be qualified and trained in the technique of performing anesthesia, should be familiar with the diagnosis and treatment of systemic toxic reactions, adverse events and reactions, and other complications.

Lidocaine should be used with caution in patients with myasthenia gravis gravisEpilepsy, chronic heart failure, bradycardia and respiratory depression, and in combination with drugs that interact with lidocaine and leading to increase its bioavailability, potentiation effects (e.g., phenytoin) or elongation excretion (e.g., hepatic or renal disease, while which can accumulate metabolites of lidocaine).

For patients receiving antiarrhythmic drugs III class (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.

Conduction 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, because local anesthetics can depress AV-conducting;

- 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.

Lidocaine injection 10 mg / ml, 20 mg / ml is not allowed for intrathecal administration (subarachnoidal anesthesia).

Effect on the ability to drive transp. cf. and fur:

Depending on the dose and mode of administration lidocaine can have a temporary effect on motor ability and coordination. During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for injection, 10 mg / ml and 20 mg / ml.

Packaging:

5 ml and 10 ml of the drug at a dosage of 10 mg / ml, 2 ml, 5 ml, 10 ml of the drug at a dosage of 20 mg / ml in ampoules of colorless glass of grade HC-1 and HC-3.

10 ampoules in boxes of cardboard.

5 ampoules in contour cell packs from polyvinylchloride film and aluminum foil printed lacquered, or without foil.

1 or 2 contour squares per 5 ampoules in a pack of cardboard.

Each instruction pack or box is supplied with instructions for use, the ampoule scaler.

When using ampoules with a kink ring or with a notch and a dot the ampoule scaper is not inserted.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003673

Date of registration:14.06.2016

Expiration Date:14.06.2021

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp26.02.2018

Illustrated instructions

Instructions

Lidocaine (Lidocaine)