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

Pharmacodynamics:Lidocaine is a local anesthetic of the amide type. Lidocaine reversibly blocks impulses in nerve fibers of sensitive neurons, inhibiting the transport of sodium ions through the neuron membrane, thereby providing local anesthetic action. Similar effects are also observed on excitable membranes of the brain and cardiac muscle. Lidocaine has a rapid onset of action, high anesthetic activity and low toxicity. In lower concentrations lidocaine has less influence on motor nerve fibers.With topical application dilates blood vessels, does not have a locally irritating effect.

Pharmacokinetics:

The rate of absorption depends on the dose, route of administration and blood supply to the injection site. Intercostal blockade leads to the greatest plasma concentration (about 1.5 μg / ml when 100 mg is administered), whereas subcutaneous administration to the abdomen shows the lowest plasma concentration (of the order of 0.5 μg / ml when 100 mg is administered). The volume of distribution in the equilibrium state is 91 liters, and the connection with plasma proteins, predominantly with α₁acid glycoprotein, 65%.

Absorption from the epidural space is complete and biphasic with a half-life of about 9.3 and 82 minutes, respectively. Slow absorption is a time-limiting factor in the elimination of lidocaine, which explains the slower elimination after epidural injection than after intravenous administration.

Elimination of lidocaine is mainly due to metabolism, mainly by dealkylation to monoethylglizinexylidide (MEGC) mediated by isoenzymes CYP1A2 and CYP3A4. MEGC is metabolized to 2,6-dimethylaniline and glycinexylidide (HA). Further isoenzyme CYP2D6 converts 2,6-dimethylalanine to 4-hydroxy-2,6-dimethylalanine, which is the main metabolite of urine (80%) and is released as a conjugate. MEGC has a seizure activity similar to lidocaine, whereas HA does not have such activity. The plasma concentration of MEGCs is comparable to that of the parent compound. The rate of elimination of lidocaine and MEGC after intravenous bolus administration is about 1.5-2 hours and 2.5 hours, respectively. Due to rapid metabolism in the liver, kinetics is susceptible to all violations of liver function. In patients with hepatic insufficiency, the half-life can be doubled. Renal failure does not affect kinetics, but can increase the accumulation of metabolites.

Lidocaine penetrates the placental barrier, the concentration of unbound lidocaine in Plasma of the mother and fetus are the same. However, the total plasma concentration in the fetus is lower due to a lower connection with plasma proteins.

Indications:Local anesthesia: intravenous regional anesthesia, infiltration anesthesia, conductive (nerve blockade), epidural anesthesia, spinal (lumbar) anesthesia.

Contraindications:

Hypersensitivity to local anesthetics of the amide type or to any auxiliary substance of the preparation.

Syndrome of weakness of the sinus node, pronounced bradycardia, atrioventricular blockade of II-III degree (except when the probe is inserted for stimulation of the ventricles), sinoatrial block, Wolff-Parkinson-White syndrome, acute and chronic heart failure (III-IV functional class), cardiogenic shock, Morgagni-Adams-Stokes syndrome, intraventricular conduction disorders.

Lidocaine is not allowed to be used for epidural anesthesia in patients with severe arterial hypotension or with cardiogenic or hypovolemic shock.

It is also necessary to take into account the general contraindications to the conduct of a particular type of anesthesia.

Carefully:Chronic heart failure (I-II functional class), arterial hypotension, hypovolemia, atrioventricular blockade of the I degree; in patients who received antiarrhythmics III class (for example, amiodarone), they should be carefully monitored and monitored by the ECG, since the cardiac effects of lidocaine and class III antiarrhythmics can be summarized (see below).section "Interaction with other medicinal products"); sinus bradycardia, severe hepatic and / or renal failure, myasthenia gravis, epileptiform convulsions (including history), in patients with impaired respiratory function in frail or elderly (over 65 years).

Pregnancy and lactation:

Pregnancy

Adequate data on the treatment of pregnant women are absent.

Lidocaine penetrates the placenta. Lidocaine was used in a large number of pregnant women and women of childbearing age. These violations of lidocaine reproductive processes (eg, increase in the frequency of malformations or any direct or indirect effects on the fetus) are absent. However, the risk to humans is not fully established. Studies on animals regarding the effect of lidocaine on pregnancy, embryo-fetal development, childbirth and postnatal development are incomplete.

For short-term use during pregnancy and childbirth, the benefit to the mother should exceed the risk to the fetus. Paracervical lidocaine or pudendal blockade increases the risk of such reactions in the fetus, as bradycardia or tachycardia.In connection with this, it is necessary to control the fetal heart rate (see the section "Pharmacokinetics"),

Breast-feeding

A small amount of lidocaine penetrates into breast milk. When used in recommended doses, the effect on the baby is unlikely. Nevertheless, caution should be exercised when lidocaine is used in nursing mothers.

Dosing and Administration:

Lidocaine is administered intravenously, intramuscularly, subcutaneously or epidurally. Lidocaine It is allowed to apply only to doctors (or under their supervision), having experience of carrying out regional anesthesia. It is necessary to enter the smallest dose, which causes the desired effect.

The method of lidocaine administration depends on the type of anesthesia (intravenous regional anesthesia, infiltration anesthesia, nerve blockade and epidural anesthesia).

The effect of lidocaine can be prolonged by the addition of 0.1% epinephrine solution (0.1 ml per 20 ml lidocaine).

Adults

The maximum recommended dose of lidocaine with adrenaline (epinephrine) should not exceed 7 mg / kg of body weight, the maximum recommended total dose should not exceed 500 mg. When used without adrenaline, the maximum individual dose should not exceed 4.5 mg / kg of body weight,the maximum recommended total dose should not exceed 300 mg.

Infiltration anesthesia (intramuscularly, intradermally, subcutaneously) - 0.125%, 0.25%, 0.5% solutions are used; To achieve infiltration anesthesia, up to 60 ml of 0.5% solution or up to 30 ml of 1% solution is used.

For conductive anesthesia (anesthesia of peripheral nerves, including with blockade of nerve plexuses) perineurally 1 and 2% solutions are used; the maximum total dose is up to 400 mg (40 ml of a 1% solution and 20 ml of a 2% solution of lidocaine). For blockade of nerve plexuses - 10-20 ml of 1% solution or 5-10 ml of 2% solution.

Epidural anesthesia (epidural) - 25-30 ml (250-300 mg) of 1% solution is used for the preparation of analgesia; to obtain anesthesia 15-20 ml (225-300 mg) 1.5% solution or 10-15 ml (200-300 mg) of 2% solution; for thoracic epidural anesthesia - 20-30 ml (200-300 mg) of 1% solution. 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.

Spinal anesthesia: subarachnoid, 3-4 ml of solution of 2% solution (60-80 mg).

When using caudal anesthesia (epidural, in the sacral canal): in obstetrical practice 200-300 mg (10-15 ml) 2% solution; in surgical practice - 15-20 ml (225-300 mg) of 1.5% solution.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. For intravenous regional anesthesia, 10-60 ml (50-300 mg) of 0.5% solution. For conductive anesthesia of peripheral nerves (perineural): humerus 15-20 ml (225-300 mg) 1.5% solution; in dental practice - 1-5 ml (20-100 mg) of 2% solution; blockade of intercostal nerves - 3 ml (30 mg) of 1% solution.

Paracervical anesthesia (for mucous membranes) - 10 ml (100 mg) of 1% solution in each side, if necessary, repeated administration is possible in not less than 1.5 hours.

Paravertebral anesthesia (paravertebral) - 3 to 5 ml (30-50 mg) of 1% solution.

Retrobulbaric anesthesia (retrobulbarno) - 3-5 ml (120-200 mg) of 4% solution, 3-4 ml of 2% solution.

Parabulbar anesthesia (parabulbar) - 1 -2 ml of a 2% solution.

Local infiltration (subconjunctival) anesthesia - 0.5-1.0 ml of 2% solution. Vagosimpathetic blockade (in the fiber around the neurovascular bundle corresponding to the localization): cervical (stellate) - 5 ml (50 mg) of 1% solution, lumbar - 5-10 ml (50-100 mg) of 1% solution.

Trans-tracheal anesthesia - 2-3 ml (80-120 mg) of 4% solution, possibly combined with local intra-pharyngeal administration of 4% solution in the form of a spray, the maximum dose in this case should not exceed 5 ml (200 mg) or 3 mg / kg.

The maximum dose for adults is no more than 4.5 mg / kg or 300 mg; for intravenous regional anesthesia - no more than 4 mg / kg. In children and weakened patients, the dose is reduced. Children

The maximum dose for children varies according to age and weight.

For example, in a 5-year-old child weighing 50 kg, the dose of lidocaine should not exceed 75-100 mg (1.5 to 2 mg / kg). When using the drug in more dilute solutions (for example, from 0.25 to 0.5%), the total dose should not exceed 3 mg / kg.

Older children

Recommended dosages for children with neuromuscular blockade are up to 4.5 mg / kg 0.25-1% solution, with intravenous regional anesthesia 3 mg / kg 0.25-0.5% solution.

The maximum dose for children is 4.5 mg / kg.

When used in children, the lowest effective concentration and the lowest effective dose of the drug should be used. For dilution, 0.9% sodium chloride solution for injection is used.

Repeated administration within 24 hours is not recommended.

Side effects:Undesirable reactions caused by lidocaine are often difficult to distinguish from the physiological effects of nerve blockade (eg, lowering blood pressure, bradycardia) and conditions caused by direct administration (eg, nerve damage) or indirectly (eg, epidural abscess).

Often (>1/10)	From the side of the vessels	Reduction of blood pressure
Often (>1/10)	From the gastrointestinal tract	Nausea
Often (>1/100, <1/10)	From the nervous system	Paresthesia, dizziness
	From the heart	Bradycardia
	From the side of the vessels	Increased blood pressure
	From the gastrointestinal tract	Vomiting
Infrequently (>1/1000, <1/100)	From the nervous system	Peripheral paresthesia, numbness of the tongue, hyperacusis, tinnitus, visual impairment, drowsiness, loss of consciousness, tremor, convulsions, dysarthria
Rarely (>1/10 000, <1/1000)	From the nervous system	Neuropathy, peripheral nerve damage, arachnoiditis
	From the heart	Cardiac arrest, arrhythmia
	On the part of the respiratory system, the organs of the thorax and the mediastinum	Respiratory failure, paralysis of the respiratory muscles
	From the immune system	Hypersensitivity reactions, hives, rash, angioedema, in severe cases - anaphylactic shock
	From the side of the organ of vision	Doubling in the eyes

Overdose:Unintentional intravascular injection of local anesthetics can cause severe systemic toxicity (from a few seconds to several minutes).Signs of systemic toxicity due to an overdose appear later (15-60 minutes after administration), which is due to a slower increase in the concentration of local anesthetic in the blood (see section "Side effect"). When symptoms of systemic toxicity appear, the administration should be stopped immediately.

Symptoms

Excitation of the central nervous system, followed by its oppression. With the introduction of large doses, the first symptom is the rapid onset of seizures. Anxiety, dizziness, visual impairment, perioral paresthesia, nausea. Then ataxia, auditory disorders, euphoria, confusion, difficulty speaking, pallor, sweating, tremors, convulsions, coma, stopping breathing. Arrhythmias, mainly bradyarrhythmias, but at high doses also ventricular tachycardia, ventricular fibrillation, expansion of the QRS complex, AV blockade. Heart failure, lowering of arterial pressure (in some cases methemoglobinemia is described).

Treatment

In case of an overdose, it is necessary to take urgent measures to maintain blood circulation and breathing and control seizures.It is necessary to provide airway patency, start the introduction of oxygen, if necessary - artificial ventilation of the lungs. Hemodynamics is maintained by administering plasma or plasma-substituting solutions, dobutamine and, if necessary, norepinephrine (starting at a dose of 0.05 μg / kg / min, increasing, if necessary, 0.05 μg / kg / min every 10 min), in severe cases of monitoring hemodynamics. Possible use of ephedrine. Control of convulsions is established by intravenous diazepam or thiopental sodium, taking into account that anticonvulsants can inhibit respiration and circulation. With bradycardia, the administration of atropine is possible. When cardiac arrest, standard resuscitation measures are performed.

The effectiveness of hemodialysis in acute overdose of lidocaine is negligible.

Interaction:

Drugs that inhibit the metabolism of lidocaine (for example, cimetidine), can lead to potentially toxic concentrations of the latter if lidocaine was administered multiple times in high doses or for an extended period of time.Such interactions are not clinically relevant for short-term treatment with lidocaine at recommended doses.

Lidocaine should be used with caution with other local anesthetics or Class IB antiarrhythmic drugs, because of the potential effects of summation.

Separate studies of the drug interactions of local anesthetics with

Class III antiarrhythmics (for example, amiodarone) have not been performed, it is recommended that

caution (see section "Special instructions"),

Lidocaine is incompatible with solutions of amphotericin B, sulfadiazine, methohexital and phenytoin.

Stable in an acidic environment, drugs, for example, epinephrine, norepinephrine and isoprenaline after a few hours of being in the lidocaine solution begin to degrade, since lidocaine can increase the pH of the resulting solution above the pH needed for the stability of these substances.

Alkalization can lead to the formation of a precipitate of lidocaine, since the latter is poorly soluble at pH> 6.5.

Special instructions:

With the exception of the simplest procedures, in carrying out procedures for regional and local anesthesia, it is necessary to have ready equipment for resuscitation.With any major blockade, an intravenous cannula should be inserted prior to the administration of the anesthetic. Like other local anesthetics, lidocaine can cause acute toxic effects from the central nervous and cardiovascular systems, if its application leads to high plasma concentrations, especially with significant intravascular injection. Epidural anesthesia can lead to severe undesirable reactions, for example, depression of the cardiovascular system, especially with concomitant hypovolemia. In case of cardiovascular damage, care should be taken in all cases. The main causes of traumatic nerve damage and (or) local toxic effects on muscles and nerves is the introduction of a local anesthetic. The extent of such lesions depends on the size of the injury, the concentration of the local anesthetic and the duration of the local anesthetic effect on the tissue. In this regard, it is necessary to administer the lowest effective dose.

Significant intravascular injections in the head and neck can cause symptoms from the brain even in low doses.

The action of local anesthetics is reduced when injected into the inflamed or infected areas.

With epidural administration of anesthetic, it is possible to lower blood pressure and bradycardia. The risk is reduced by intravenous administration of crystalloid or colloidal solutions. Reduction of blood pressure should be cured, for example, by

5-10 mg of ephedrine intravenously, repeating the administration if necessary.

When lidocaine is injected into the muscle, the plasma activity of creatine phosphokinase may increase, which may make it difficult to diagnose acute myocardial infarction. Porphyrogenic activity of lidocaine is not excluded, therefore, its administration to patients with acute porphyria should be carried out only in the absence of other alternatives. Strict caution is necessary in all patients with porphyria.

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 20 mg / ml.

Packaging:2 ml per ampoule of colorless transparent glass with a break point. For each ampoule a label is applied or labeled with a quick-fixing paint. 10 ampoules per blister of PVC, 1 or 10 blisters together with instructions for use in a pack of cardboard. For 5 ampoules in a blister of PVC, 2 or 20 blisters together with instructions for use in a pack of cardboard.

Storage conditions:Store in a 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.

Terms of leave from pharmacies:On prescription

Registration number:LP-002505

Date of registration:17.06.2014/29.12.2014

Date of cancellation:2019-06-17

The owner of the registration certificate:ALVILS, LTD. ALVILS, LTD. Russia

Manufacturer: & nbsp

NORTH CHINA PHARMACEUTICAL CORPORATION China

Information update date: & nbsp09.04.2016

Illustrated instructions

Instructions

Lidocaine (Lidocain)