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

Excipients: sodium chloride - 8.0 mg, 0.1 M sodium hydroxide solution or 0.1 M hydrochloric acid solution to pH 4.0-6.5, water for injection - up to 1.0 ml.

Description:A clear, colorless liquid.

Pharmacotherapeutic group:Local anesthetic

ATX: & nbsp

N.01.B.B.01 Bupivacaine

Pharmacodynamics:

Bupivacaine is a local anesthetic of a long-acting amide type. Reversibly blocks the impulses through the nerve fiber, disrupting the transport of sodium ions through the sodium channels. May have a similar effect in the brain and myocardium.

The most characteristic feature of bupivacaine is the duration of its action, which is not strongly dependent on the addition of epinephrine to it. Bupivacaine is the drug of choice for continuous epidural anesthesia. At low concentrations, it has less effect on motor fibers and has a shorter duration of action, which is useful for short-term pain relief, for example, during labor or after an operation.

The relative density of the drug solution is 1004 at 20 ° C (equivalent to 1000 at 37 ° C, gravity has little effect on its spread in the subarachnoid space.) Subarachnoidal administration introduces a small dose, resulting in a relatively low concentration and short duration blockade.With subarachnoidal administration of bupivacaine, which does not contain dextrose, anesthesia is less predictable, but longer than with the administration of a solution of bupivacaine containing dextrose.

Pharmacokinetics:

The pKa value of bupivacaine is 8.2, the partition coefficient is 346 (at 25 ° C in n-octanol / phosphate buffer pH 7.4).

The rate of absorption depends on the dose, route of administration and blood supply at the injection site. With intercostal blockade due to rapid absorption, the maximum concentration in blood plasma is 4 mg / l (with 400 mg), with subcutaneous injections in the abdomen, plasma concentrations are lower. In children with caudal blockade, there is rapid absorption and a high plasma concentration is achieved - about 1-1.5 mg / l (with 3 mg / kg body weight).

Bupivacaine is completely absorbed into the blood from the epidural space, the absorption is biphasic, the half-life for the two phases is 7 minutes and 6 hours, respectively. Slow absorption limits the elimination rate of bupivacaine, which explains the longer half-life after introducing it into the epidural space than with intravenous administered.

The equilibrium distribution of bupivacaine volume is 73 l, the hepatic extraction ratio - 0.4, total plasma clearance - 0.58 l / min and the half-life of plasma -. 2.7 h half-life of the newborn can be longer compared with adults - up to 8 hours. In children older than 3 months, the elimination half-life is equal to that of adults.

The pharmacokinetics of bupivacaine in children is similar to its pharmacokinetics in adults.

The connection with plasma proteins is 96%, mainly with a iacid plasma glycoproteins. After major operations, the concentration of this protein can be increased, which may lead to a higher overall concentration of bupivacaine in the plasma. The free fraction of bupivacaine does not change. Therefore, the potentially toxic plasma concentration is well tolerated.

Bupivacaine is almost completely metabolized in the liver, mainly by aromatic hydroxylation to 4-hydroxybupivacaine and N-dezalkilirovaniya to 2,6-pipekoloksilidina (RSC), the two reactions are catalyzed isoenzyme cytochrome CYP3A4. Thus, the clearance depends on the hepatic blood flow and the activity of the metabolizing enzymes.

Bupivacaine penetrates the placenta, the concentration of unbound bupivacaine in the fetus is equal to the maternal. In view of the lower association with plasma proteins in the fetus, the total plasma concentration is lower.

With intrathecal administration

Bupivacaine is well soluble in lipids with a partition coefficient between oil and water equal to 27.5.

Bupivacaine is completely absorbed from the subarachnoid space into two phases with a half-life of 50-400 minutes. Slow absorption is the limiting factor in the elimination of bupivacaine, which explains its longer half-life than with intravenous administration.

Absorption from the subarachnoid space is slow, which, combined with the administration of a low dose required for spinal anesthesia, results in a relatively low maximum plasma concentration (0.4 mg / L for every 100 mg administered).

Indications:

- Surgical anesthesia in adults and children over 12 years of age;

- Acute pain in adults and children over 1 year old;

- non-filtration anesthesia, when a long-term anesthetic effect is required, for example, in post-operative pain;

- conductive anesthesia with a prolonged effect or epidural anesthesia in cases where the addition of epinephrine is contraindicated and undesirable significant relaxation of the muscles;

anesthesia in obstetrics.

With intrathecal administration

Spinal anesthesia during surgical operations on the lower extremities, including operations on the hip joint, lasting 3-4 hours and not requiring a pronounced motor block.

Contraindications:

- Hypersensitivity to any of the components of the drug or to other local anesthetics of the amide type;

- severe arterial hypotension (cardiogenic or hypovolemic shock);

- Children's age: up to 12 years with surgical anesthesia, up to 1 year: for all indications for use, with the exception of intrathecal anesthesia, in which the drug allowed to enter at birth;

- intravenous regional anesthesia (Bira blockade) (accidental penetration of bupivacaine into the bloodstream can cause the development of acute systemic toxic reactions);

- Paracervical blockade in obstetrics.

States, which are contraindications for conducting epidural or intrathecal anesthesia:

- diseases of the central nervous system (CNS) (eg, meningitis, tumors, poliomyelitis, intracranial hemorrhage);

- purulent skin infections at or near the lumbar puncture;

- spinal stenosis, active diseases (eg, spondylitis, tumors, tuberculosis) or trauma (for example, fracture) of the spine;

- sepsis, subacute combined degeneration of the spinal cord due to pernicious anemia and tumors of the brain and spinal cord;

- cardiogenic or hypovolemic shock;

- a clotting disorder or active anticoagulant therapy.

Carefully:

Cardiovascular insufficiency (possibly progression), heart block, inflammatory diseases or infection of the injection site (with infiltration anesthesia), cholinesterase deficiency, renal insufficiency, elderly age (over 65 years), late pregnancy (III trimester, see "Application during pregnancy and during breastfeeding "and" Special instructions "), general severe condition, decreased hepatic blood flow (eg, in chronic heart failure, liver diseases), simultaneous on The values antiarrhythmic drugs (including beta-blockers), children (1-12 years).

Bupivacaine should be used with caution in patients receiving other local anesthetics or preparations structurally similar to local anesthetic agents of the amide type, such as antiarrhythmics (eg, lidocaine, mexiletine).

Pregnancy and lactation:

The use of bupivacaine to achieve paracervical obstruction in obstetrics can cause severe cardiovascular disorders in the fetus, such as bradycardia / tachycardia. The use of bupivacaine as a means for paracervical blockade is contraindicated (see section "Contraindications"). The use of the drug according to the declared indications for use is possible if the expected benefit for the mother exceeds the possible risk to the fetus.

Bupivacaine penetrates into breast milk, but when applied in therapeutic doses, the effect on the baby is negligible.

With intrathecal administration

Data on adverse effects on pregnancy are absent. When used in pregnant animals in large doses, a decrease in the survival of offspring in rats and embryotoxic effects in rabbits were found. Concerning bupivacaine should not be used in the early stages of pregnancy, unless the benefits exceed the risks.

In late pregnancy, the dose should be reduced (see section "Special instructions").

Bupivacaine penetrates into breast milk, but when applied in therapeutic doses, the effect on the baby is negligible.

Dosing and Administration:

Use bupivacaine can only doctors who have experience of local anesthesia or under their supervision. To achieve the required degree of anesthesia, the minimum possible dose should be administered.

Under no circumstances should you allow accidental intravascular drug administration. It is recommended to perform an aspirate test before and during the administration of the drug. The drug should be administered slowly, at a rate of 25-50 mg / min or fractional, maintaining continuous verbal contact with the patient and controlling the heart rate. During epidural administration, a dose of 3-5 ml of bupivacaine with epinephrine is preset. With a random intravascular injection, there is a short-term increase in the heart rate, with a random intrathecal injection, a spinal block appears.If there are toxic signs, the administration is immediately stopped.

Below are the estimated doses that need to be corrected depending on the depth of anesthesia and the patient's condition.

Infiltration anesthesia: 5-60 ml of the drug at a concentration of 2.5 mg / ml (12.5-150 mg bupivacaine) or 5-30 ml of the drug at a concentration of 5 mg / ml (25-150 mg bupivacaine).

Diagnostic and therapeutic blockade: 1-40 ml of the drug at a concentration of 2.5 mg / ml (2.5-100 mg bupivacaine), for example, blockade of the trigeminal nerve 1-5 ml of the drug (2.5-12.5 mg of bupivacaine) and cervico-thoracic node of sympathetic trunk 10-20 ml of the drug (25-50 mg of bupivacaine).

Intercostal blockade: 2-3 ml of the drug at a concentration of 5 mg / ml (10-15 mg of bupivacaine) per nerve, not exceeding the total amount - 10 nerves.

Major blockades (eg, epidural block, blockade of the sacral or brachial plexus): 15-30 ml of the drug in a concentration of 5 mg / ml (75-150 mg of bupivacaine).

Anesthesia in Obstetrics (eg, epidural and caudal anesthesia with natural delivery): 6-10 ml of the drug at a concentration of 2.5 mg / ml (15-25 mg of bupivacaine) or 6-10 ml of the drug at a concentration of 5 mg / ml (30-50 mg of bupivacaine).

Every 2-3 hours, repeated administration of the drug in the initial dose is allowed.

Epidural anesthesia with caesarean section: 15-30 ml of the drug in a concentration of 5 mg / ml (75-150 mg of bupivacaine).

Epidural analgesia in the form of intermittent bolus injection: initially inject 20 ml of the drug at a concentration of 2.5 mg / ml (50 mg bupivacaine), then every 4 to 6 hours, depending on the number of damaged segments and the patient's age, 6-16 ml of the drug at a concentration of 2.5 mg / ml (15 -40 mg of bupivacaine).

Epidural analgesia in the form of continuous infusion (for example, postoperative pain):

Type of blockade	Concentration	Scope	Dose
Epidural introduction (at the lumbar level):
Bolus ¹	2.5 mg / ml	5-10 ml	12.5-25 mg
Infusion	2.5 mg / ml	5-7.5 ml / hr	12.5-18.75 mg²
Epidural introduction (at the thoracic level):
Bolus ¹	2.5 mg / ml	5-10 ml	12.5-25 mg
Infusion	2.5 mg / ml	2.5-5 ml / h	6.25-12.5 mg
Epidural introduction (natural delivery):
Bolus ¹	2.5 mg / ml	6-10 ml	15-25 mg
Infusion	2.5 mg / ml	2-5 ml / hr	5-12.5 mg

¹If during the previous hour the drug was not administered bolus.

²Do not exceed the maximum recommended daily dose (see below).

During the surgical intervention, additional administration of the drug is possible.

With the simultaneous use of narcotic analgesics, the dose of bupivacaine should be reduced.

With prolonged administration of the drug, the patient should regularly monitor blood pressure, heart rate and other signs of potential toxicity. When toxic effects occur, the administration of the drug is necessary immediately stop.

During the surgical intervention, additional administration of the drug is possible.

With the simultaneous use of narcotic analgesics, the dose of bupivacaine should be reduced.

With prolonged administration of the drug, the patient should regularly monitor blood pressure, heart rate and other signs of potential

Recommended maximum doses

The maximum recommended single dose, calculated at 2 mg / kg body weight, is 150 mg for adults for four hours. This is equivalent to 60 ml of the drug at a concentration of 2.5 mg / ml (150 mg bupivacaine) and 30 ml drug at a concentration of 5 mg / ml (150 mg bupivacaine).

The maximum recommended daily dose is 400 mg. However, when calculating the total daily dose, it is necessary to take into account the patient's age, physique and other significant conditions.

Children aged 1-12 years

Regional anesthesia should be performed by a doctor who has experience working with children and who has the appropriate technique of administration.

Doses in children, given in the table, are indicative. Variability is possible. Children with high body weight, as a rule, need to reduce the dose, based on the ideal body weight. In determining the methods of anesthesia and taking into account the individual characteristics of patients should use the generally accepted guidelines for anesthesia.

It is necessary to enter the minimum dose necessary to achieve sufficient anesthesia.

	Concentration, mg / ml	Volume, ml / kg	Dose, mg / kg	Start actions, mines	Duration of action, h
Acute pain
Caudal epidural anesthesia	2,5	0,6-0,8	1,5-2	20-30	2-6
Lumbar epidural anesthesia	2,5	0,6-0,8	1,5-2	20-30	2-6
Thoracic epidural anesthesia^b)	2,5	0,6-0,8	1,5-2	20-30	2-6
Regional blockade (eg, blockade and infiltration of small nerves)	2,5		0,5-2
	5		0,5-2
Blockade peripheral nerves (for example, blockade of the iliac-inguinal / iliac-hypogastric nerves)	2,5		0,5-2	a)
	5		0,5-2	a)

a) the beginning and duration of peripheral nerve blockage depends on the nature of the blockade and dose

(b) with thoracic epidural anesthesia, the drug is administered in ever increasing doses to achieve the desired level of anesthesia.

The dose in children is calculated based on 2 mg per kg of body weight.

In order to prevent the drug from entering the vascular bed, the aspiration test should be performed before and during the administration of the main dose. The drug should be administered slowly, dividing the total dose into several injections, especially with lumbar and thoracic epidural anesthesia, continuously observing the indicators of vital organs.

Peritonsillar infiltration anesthesia in children from 2 years of age: in a dose of 7.5 mg and 12.5 mg per tonsil with a concentration of bupivacaine 2.5 mg / ml.

Blockade of ilio-inguinal / ilio-hypogastric nerves in children from 1 year old: 0.1-0.5 ml / kg with a concentration of bupivacaine 2.5 mg / ml, which is equivalent to 0.25-1.25 mg / kg body weight.

For children aged 5 years and older, the drug can be administered in a concentration of bupivacaine 5 mg / ml, equivalent to 1.25-2 mg / kg.

Blockade of the penis: 0.2-0.5 ml / kg with a concentration of bupivacaine 5 mg / ml, equivalent to 1.0-2.5 mg / kg.

Data on epidural anesthesia in children (bolus or continuous administration) are limited.

Cooking method

If a solution with a concentration of 2.5 mg / ml is required, it is possible to dilute the preparation at a concentration of 5 mg / ml only with compatible solvents, such as a 0.9% sodium chloride solution for injection, since the properties of the preparation may change after dilution, which may lead to precipitation.Breeding should be carried out only by qualified personnel with mandatory visual control before use. It is possible to use only clear solutions without visible particles.

The drug solution is intended for single use only.

With intrathecal administration

Use bupivacaine can only doctors who have experience in conducting local anesthesia or under their supervision. To achieve the required degree of anesthesia, the minimum possible dose should be administered.

The doses given below are adults. Selection of the dose is carried out individually.

Elderly patients and Patients in late pregnancy The dose should be reduced.

Indications for use	Dose, ml	Dose, mg	Start actions	Duration actions
Surgical operations on the lower extremities, including operations on the hip joint	2-4 ml	10-20 mg	5-8 min	1,5-4 hours

The recommended injection site is at the level of L3.

Clinical experience with a dose exceeding 20 mg is not available. Prior to the administration of the drug, intravenous access should be provided.

The introduction is carried out only after confirmation of the entry into the subarachnoid space (the flow out of the needle of the transparent cerebrospinal fluid or during aspiration).If an unsuccessful attempt is made, only one additional attempt should be made at a different level and less. One of the reasons for the lack of effect can be a poor distribution of the drug in the subarachnoid space, which can be corrected by changing the patient's position.

Children with body weight less than 40 kg

Bupivacaine, an injection for injection, 5 mg / ml, may be used in children.

The main difference between adults and children is that in newborns and infants the volume of cerebrospinal fluid is greater, that to achieve the same degree of blockade requires a relatively high dose per kilogram of body weight in comparison with adults.

Regional anesthesia should be performed by a doctor who has experience working with children and who has the appropriate technique of administration.

Doses in children, given in the table, are indicative. Variability is possible. In determining the methods of anesthesia and taking into account the individual characteristics of patients, general guidelines on anesthesia. It is necessary to enter the minimum dose necessary to achieve sufficient anesthesia.

Body weight, kg	Dose, mg / kg
<5	0,4-0,5 mg / kg
5-15	0,3-0,4 mg / kg
15-40	0,25-0,3 mg / kg

Side effects:

The frequency of adverse reactions is determined by the following categories: Often (≥1/10), often (≥1/100 - <1/10), infrequently (≥1/1 000 - <1/100), rarely (≥1/10 000 - <1/1 000), rarely (<1/10 000).

Undesirable drug-induced drug reactions may be difficult to distinguish from the physiological manifestations of nerve blockade (eg, lowering blood pressure, bradycardia), reactions, directly (eg, nerve damage) or indirectly caused by administration (eg, epidural abscess), leakage reactions spinal fluid (eg, post-puncture headache)

Neurological disorders are a rare but well-known undesirable drug reaction caused by local anesthesia, especially with epidural and intrathecal administration of the drug.

Symptoms and tactics of conducting an acute toxicity system are described in the section "Overdose".

From the immune system: rarely - allergic reactions, anaphylactic shock.

From the nervous system: often - Paresthesia, dizziness; infrequently - signs of toxicity from the central nervous system: convulsions, paresthesia in the mouth, numbness of the tongue, hyperacusis, visual impairment, loss consciousness, tremor, mild dizziness, tinnitus, dysarthria; rarely - neuropathy, peripheral nerve damage, arachnoiditis, paresis, paraplegia.

From the side of the organ of vision: rarely - Diplopia.

From the heart: often bradycardia; rarely - cardiac arrest, arrhythmia.

From the side of the vessels: Often - lowering blood pressure; often - increase in blood pressure.

On the part of the respiratory, thoracic and mediastinal organs: rarely - respiratory depression.

From the gastrointestinal tract: Often - nausea; often - vomiting.

From the side of the kidneys and urinary tract: often - retention of urine.

Undesirable reactions in children similar to those of adults, however, early signs of local anesthetic toxicity in children are more difficult to recognize if the blockade is performed under sedation or anesthesia.

With intrathecal administration

From the side of the cardiovascular system: Often - reduction of blood pressure, bradycardia; rarely - cardiac arrest.

From the gastrointestinal tract: Often - nausea, often - vomiting.

From the nervous system: often - headache after puncture of the dura mater; infrequently - Paresthesia, paresis, dysesthesia; rarely - complete unintentional spinal block, paraplegia, paralysis, neuropathy, arachnoiditis.

From the side of the kidneys and urinary tract: often - urinary retention, incontinence.

From the side of skeletal muscles, connective tissue and bones: infrequently - muscle weakness, back pain.

From the immune system: rarely - Allergic reactions, anaphylactic shock. On the part of the respiratory system: rarely - respiratory depression.

Undesirable reactions in children are similar to those in adults, however, early signs of local anesthetic toxicity in children are more difficult to recognize if the blockade is performed under sedation or anesthesia.

Overdose:

Acute systemic intoxication

Symptoms

Toxic reactions are manifested mainly from the central nervous and cardiovascular systems. They arise due to the high concentration of local anesthetic in the blood, which can be caused by accidental intravascular injection, overdose or exceptionally rapid absorption from the area of highly vascularized tissues.section "Special instructions").

Symptoms of CNS damage for all local anesthetics of the amide type are similar, whereas the symptoms of cardiovascular damage differ qualitatively and quantitatively.

Unintentional intravascular injection of a local anesthetic can lead to immediate systemic toxic reactions (within a few seconds-minutes). Signs of systemic toxicity in case of an overdose appear later (15-60 min after administration), as the local anesthetic concentration in the blood rises slowly.

From the central nervous system

Intoxication of the central nervous system manifests itself gradually. The initial signs of intoxication, as a rule, are: paresthesia around the mouth, dizziness, numbness of the tongue, hyperacusis, tinnitus, visual impairment. More serious manifestations are dysarthria and myofasciculation, which may precede the onset of generalized seizures. These phenomena should not be mistaken for a neurotic disorder. Following them, loss of consciousness and the development of a large convulsive fit lasting from a few seconds to several minutes are possible.In connection with increased muscular activity and insufficient ventilation (disruption of the normal breathing process), hypoxia and hypercapnia rapidly build up during seizures. In severe cases, breathing may stop. Concomitant acidosis increases the toxic effect of local anesthetics.

The resolution of symptoms is due to the metabolism of the local anesthetic and its redistribution from the central nervous system. The described phenomena quickly stop, if the overdose was not excessive.

From the side of the cardiovascular system

The defeat of the cardiovascular system, as a rule, indicates more severe intoxication. It is usually preceded by signs of CNS damage that can be erased if the patient is in anesthesia or deep sedation caused by drugs such as benzodiazepines or barbiturates. Due to the high concentration of local anesthetics in blood plasma, there may be a drop in blood pressure, bradycardia, arrhythmias and cardiac arrest. Toxic manifestations of the cardiovascular system are often due to myocardial depression and myocardial conduction,which reduce cardiac output, lower blood pressure, atrioventricular blockade (AV blockade), bradycardia, ventricular arrhythmia, including ventricular tachycardia and ventricular fibrillation, cardiac arrest. These phenomena are often preceded by severe signs of CNS involvement, including convulsions, but in rare cases, cardiac arrest occurs without concomitant signs from the CNS. After a very rapid intravenous injection, the concentration of bupivacaine in the blood plasma can be quite high. In this case, he quickly reaches the coronary arteries, and the symptoms of circulatory disorders occur earlier than signs of CNS damage. This the mechanism causes myocardial depression and may be the first manifestation of intoxication.

When the blockade is performed under general anesthesia in children, early signs of intoxication are difficult to detect, and careful monitoring is therefore required.

Treatment

If a spinal block arises, adequate ventilation should be provided (ensure airway patency, oxygen supply, if necessary, intubation and artificial ventilation).

With a decrease in blood pressure and (or) bradycardia, it is necessary to introduce a vasopressor with inotropic action.

When symptoms of acute systemic intoxication occur, the administration of the drug should be stopped immediately.

It is necessary to ensure proper ventilation, oxygenation and maintain blood circulation.

In all cases, it is necessary to adjust the supply of oxygen, if necessary, intubation and controlled ventilation (in some cases with hyperventilation).

When convulsions are injected diazepam, with bradycardia - atropine.

With circulatory failure - dobutamine intravenously, the administration of norepinephrine (starting at 0.05 μg / kg / min if necessary with an increase in the dose of 0.05 μg / kg / min every 10 min) is allowed, in more severe cases, the dose is titrated according to the results of monitoring hemodynamics. The administration of ephedrine is possible. With severe damage to the cardiovascular system, resuscitation can continue for several hours.

Any acidosis is subject to elimination.

When managing systemic intoxication in children doses of the drug must be selected according to their age and body weight.

Interaction:

Caution should be exercised while using bupivacaine with other local anesthetics or antiarrhythmics Ib class, since they can enhance the toxic effects of each other.

A separate study of the interaction of local anesthetics and antiarrhythmic drugs of the third class (for example, amiodarone) was not carried out, nevertheless, it is advisable to use caution when using them simultaneously (see section "Special instructions"). The alkalinization can lead to precipitation, since the solubility of bupivacaine at pH> 6.5 decreases.

When preparing for the introduction, it is necessary to avoid prolonged contact of the drug with metal objects, since metal ions can cause reactions at the site of administration, which show tenderness and swelling.

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.

There are reports of cardiac arrest or death while using bupivacaine for epidural anesthesia or peripheral blockade. In some cases, resuscitation has been difficult or impossible, despite adequate treatment. Blockade of the main peripheral nerves may require the introduction of large volumes of local anesthetics into the well-blood-supplying areas of the body, often near large blood vessels. In such cases, the risk of intravascular bupivacaine or systemic absorption increases, which can lead to a high concentration of local anesthetic in the blood.

Like other local anesthetics, bupivacaine can cause acute toxic reactions from the central nervous and cardiovascular systems, if during the procedure of local anesthesia there is a high concentration in the blood. Most often this is manifested in the case of unintentional intravascular injection or with a good blood supply to the site of administration.

Certain types of local anesthesia can lead to the development of serious adverse reactions, for example:

- ePidural anesthesia, especially against hypovolemia, can lead to depression of the cardiovascular system. Care should be taken in patients with cardiovascular disease;

- PIn retrobulbar injection, the drug can occasionally enter the cranial subarachnoid space, causing temporary blindness, apnea, convulsions, collapse, and other undesirable reactions. The coping of these reactions must be carried out immediately;

- PIn the retrobulbar and peribulbar injection of local anesthetics there is a certain risk of a persistent impairment of the function of the eye muscles. The main causes are trauma and (or) local toxic effects on muscles and (or) nerves;

- with unintended intravascular injection into the head or neck area, even at low doses, the drug is able to cause cerebral symptoms. The severity of the undesirable reactions described above depends on the size of the injury, the concentration of the local anesthetic and the duration of its effect on the tissue.Therefore, as with other local anesthetics, it is necessary to administer the lowest effective dose of bupivacaine.

Caution should be exercised in patients with grade II or III AV blockade, since local anesthetics can disrupt intracardiac conduction. Care should be taken when administering the drug to elderly patients and patients with severe liver disease, severe renal failure, or a general unsatisfactory condition.

It is necessary to carry out careful monitoring and continuous ECG monitoring in patients receiving Class III antiarrhythmic drugs (for example, amiodarone), since the summation of their cardiovascular toxic effects with those of bupivacaine is possible.

When conducting epidural anesthesia, there may be a drop in blood pressure and a bradycardia. Reduce the likelihood of such complications can be through the introduction of crystalloid and colloidal solutions. With a decrease in blood pressure, immediate intravenous administration of sympathomimetics is indicated (for example, 5-10 mg of ephedrine); If necessary, repeat them.

According to the post-registration data, in some patients who received long-term local anesthetic injections into the joint cavity after the operation, chondrolisis arose. In most cases, chondrolisis of the shoulder joint. The causal relationship with the administration of bupivacaine has not been conclusively confirmed, perhaps chondrolisis is due to several factors. Contradictory data on the mechanism of the onset of this state are described in the literature. Prolonged intra-articular injection is not an approved indication for bupivacaine.

The solution does not contain preservatives, so it must be entered immediately after opening the vial. Remains of the solution are subject to destruction.

The drug contains sodium, so in the case of a salt-free diet with a limited consumption of it, you should take into account the sodium content in the preparation.

Children

The safety and effectiveness of bupivacaine in children younger than 1 year have not been studied, only limited data are available.

Data on the intra-articular blockade of bupivacaine in children 1-12 years are absent.

Data on the bupivacaine blockade of large nerves in children 1-12 years are absent.

With epidural anesthesia, the drug should be administered slowly, guided by age and body weight, since especially with epidural anesthesia at the breast level severe hypotension and respiratory failure can occur.

With intrathecal administration

Spinal anesthesia can cause severe blockade and paralysis of the intercostal muscles and diaphragm, especially in pregnant women.

Care should be taken in patients with AV blockade II and III degree, as local anesthetics can disrupt intracardiac patency. Care should be taken when administering the drug to elderly patients and patients with severe liver disease, severe renal failure or general unsatisfactory condition.

Like other local anesthetics, bupivacaine can cause acute toxic reactions from the central nervous and cardiovascular systems, if during the procedure of local anesthesia there is a high concentration in the blood.Most often this is manifested in the case of unintentional intravascular injection or with a good blood supply to the site of administration.

Against the background of a high concentration of bupivacaine in the plasma, cases of ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death were documented. At the same time, the doses used for spinal anesthesia, as a rule, do not lead to the achievement of a high systemic concentration.

A rare but serious unwanted reaction to spinal anesthesia is a high or complete spinal block, leading to cardiovascular and respiratory depression. The inhibition of the cardiovascular system, due to extensive sympathetic blockade, can lead to arterial hypotension and bradycardia or even to cardiac arrest. Respiratory depression may be due to blockade innervation of the respiratory muscles, including the diaphragm

In elderly patients and patients in late pregnancy, the risk of a high or complete spinal block, leading to oppression of blood circulation and respiration, is increased. These patients should lower the dose.

Spinal anesthesia can lead to lower blood pressure and bradycardia. This risk can be reduced by the introduction of crystalloid solutions. With a decrease in blood pressure, it must immediately be quenched, for example, by intravenous administration of 5-10 mg of ephedrine.

Neurological complications are a rare consequence of spinal anesthesia and can lead to paresthesia, anesthesia, muscle weakness and paralysis. In some cases, these complications are permanent. Care must be taken in patients with multiple sclerosis, hemiplegia, paraplegia and neuromuscular disorders. Before the start of treatment, the benefit and risk for the patient should be correlated.

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

Depending on the dose and route of administration, local anesthetics can have a transient effect on motor function and movement coordination.

Form release / dosage:Solution for injection, 5 mg / ml.

Packaging:

By 4 ml into ampoules of colorless neutral glass type I with a colored break ring or with a colored dot and a notch or without a kink ring, a colored dot and a notch.One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding can additionally be applied to the ampoules.

5 ampoules per circuit cell packaging made of polyvinylchloride film and aluminum foil foil or polymer film, or without foil and without film. Or 5 ampoules are placed in a prefabricated form (tray) made of cardboard with cells for laying ampoules.

1 or 2 contour squares or cardboard trays, together with the instructions for use and a scarifier or knife with an ampoule, or without a scarifier and an ampoule knife, are placed in a cardboard package.

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:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003590

Date of registration:26.04.2016

Expiration Date:26.04.2021

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp12.03.2017

Illustrated instructions

Instructions

Bupivacaine (Bupivacaine)