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

Pharmacodynamics:Bupivacaine - local anesthetic of long-acting amide type, 4 times stronger than lidocaine. Reversibly blocking the conductivity of pulses by nerve fibers, suppressing the transport of sodium ions through the membranes of nerve fibers. Similar effects can be observed on membranes of excitable brain cells and myocardium. Has hypotensive effect, slows heart rate.
Bupivaca is particularly suitable for prolonged epidural blockade. At a concentration of 5 mg / ml with a single epidural administration, the duration of action is 2 to 5 hours, and up to 12 hours with peripheral nerve blockade. Postoperative analgesia is maintained for 7-14 hours with intercostal blockade.
The most significant property of bupivacaine is the duration of its action. The difference between the duration of action of bupivacaine in combination with or without epinephrine is insignificant.
In low concentrations bupivacaine has a lesser effect on motor nerve fibers and has a shorter duration of action, which is useful for short-term pain relief, for example during labor or after surgery.

Pharmacokinetics:

Bupivacaine has a pKa-8.2 index of the separation coefficient of 346 (at 25 ° C in n-octanol / phosphate buffer pH 7.4).

Bupivacaine is completely absorbed into the blood from the epidural space: the absorption is biphasic, the elimination half-life for the phases is 7 minutes and 6 hours, respectively, and 50 minutes and 408 minutes (6.8 hours), respectively, with intrathecal injection.

The total plasma clearance of bupivacaine is 0.58 L / min, the volume of distribution in the equilibrium state is 73 L, the final half-life is 2.7 hours, the intermediate hepatic extraction is about 0.38 after intravenous injection. The half-life of newborns in comparison with adults may be longer - up to 8 hours. In children older than three months, the half-life is equal to that of adults. Bupivacaine, mainly binds to α1-acid plasma glycoproteins (binding to plasma proteins - 96%). After extensive surgical interventions, the level of this protein can increase and increase the concentration of bupivacaine in the blood plasma. However, the concentration of unbound bupivacaine does not change. Therefore, the concentration in the blood plasma, exceeding the toxic level, can be well tolerated.Bupivacaine clearance is almost entirely due to the metabolism of the drug in the liver and is more dependent on the activity of the liver's enzyme systems than on liver perfusion. Metabolites have less pharmacological activity than bupivacaine. Plasma bupivacaine concentration depends on the dose of bupivacaine, method of administration, vascularization in the area of administration.

During the intercostal blockade observed maximum drug concentration in blood plasma (4 mg / l after administration of a dose of 400 mg) due to rapid absorption, whereas when administered subcutaneously in the abdomen detect a minimum concentration of drug in blood plasma.

Intrathecal absorption from the subarachnoid space occurs slowly, that in combination with the administration of low dose needed for spinal anesthesia, results in a relatively low maximum plasma concentration (4 mg / l for each administration 100 mg of drug).

Slow absorption is rate-limiting and bupivacaine clearance causes longer half-life when administered epidurally preparation.

In children, rapid absorption and a high concentration in the blood plasma are observed in cases of caudal blockade (about 1.0-1.5 mg / L with a dose of 3 mg / kg body weight).

Penetrates through the placenta. The connection with plasma proteins in the fetus is lower than in the mother's body, the concentration of unbound fraction in the fetus and mother is the same. Bupivacaine is metabolized in the liver, mainly by aromatic hydroxylation to 4-hydroxy-bupivacaine and N-dealkylation to 2,6-pinecoloxylidine (RRB). Both reactions occur with the participation of cytochrome isofermite CYP3A4.

About 1% Bupivacaine is excreted urine unchanged during the day after administration and approximately 5% in the form of PPC. The concentration of PPC and 4-hydroxybupivacaine in plasma during and after prolonged bupivacaine administration is low relative to the administered dose of the drug.

In patients with liver disease, especially in patients with severe impairment of liver function, a higher risk of toxic reactions after application of local anesthetics of the amide type.

In elderly patients, the maximum analgesic and anesthetic effect occurs faster than in younger patients.Also in elderly patients there is a higher maximum concentration of bupivacaine in the blood plasma. The total plasma clearance in these patients is lowered.

Indications:

- surgical anesthesia in adults and in children older than 12 years;

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

-infiltration 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 introduction

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:

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

- the central nervous system disease (for epidural administration);

- marked arterial hypotension (cardiogenic or hypovolemic shock);

-baby age: up to 12 years with surgical anesthesia, up to 1 year with all indications for use, with the exception of intrathecal anesthesia, at which the drug is 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 (can cause fetal death).

Contraindications to epidural anesthesia:

-coagulopathy;

- Anticoagulant therapy;

- skin infection in the puncture area;

- intracranial hypertension;

-hypovolemia;

- neurological diseases, such as, for example, multiple sclerosis, meningitis, tumors, poliomyelitis, tuberculosis;

- heart disease with a fixed cardiac output (idiopathic hypertrophic subaortal stenosis, aortic stenosis, mitral stenosis, complete atrioventricular block, etc.);

-Anatomical abnormalities of the spine;

-prophylactic use of low doses of heparin.

Contraindications for intrathecal administration:

- Acute diseases of the central nervous system, such as meningitis, poliomyelitis, intracranial hemorrhage, and neoplasms of the central nervous system;

- the constriction of the spinal canal and spine disease in the exacerbation phase (spondylitis, opusol) or recent trauma (fracture) of the spine;

-septicemia;

-pernicious anemia with subacute combined degeneration of the spinal cord;

pustular lesions of the skin at the site of the proposed puncture or bordering on the puncture site;

patients with severe arterial hypotension, such as cardiogenic or hypovolemic shock;

- Coagulation disorder or concomitant anticoagulant therapy.

Carefully:Cardiovascular insufficiency (possibly progression), impaired cardiovascular function (with epidural anesthesia), weakened patients and elderly patients (over 65 years old) or patients with severe concomitant diseases such as atrioventricular blockade of grade II and III, severe hepatic or renal failure, inflammatory diseases or infection of the injection site (with infiltration anesthesia), cholinesterase deficiency, late pregnancy (III trimester), patients taking anesthesia iaritmicheskie Class III agents (e.g., amiodarone), need careful monitoring and monitoring of the ECG due to the possibility of developing adverse events from the cardiovascular system (see section "Interaction with other drugs"). The simultaneous use of bupivacaine with other local anesthetics or preparations structurally similar to local anesthetics of the amide type, such as Class I antiarrhythmic drugs (eg, lidocaine) because of the possibility of developing an additive toxic effect.
With epidural administration (caudal or lumbar anesthesia) - previous neurological diseases, septicemia, difficulty in performing a puncture due to deformity of the spine.
In case of intrathecal injection, additionally:
There is an increased risk of high or complete spinal blockage in elderly patients and in patients late in pregnancy, therefore, in such patients it is recommended to use reduced doses of the drug (see section "Dosing and Administration").
Care should be taken when conducting intrathecal anesthesia in patients with neurological diseases such as multiple sclerosis, hemiplegia,paraplegia and neuromuscular disorders, although it has not been proven that intrathecal anesthesia leads to deterioration in these diseases. Before carrying out intrathecal anesthesia in such cases, it is necessary to make sure that the potential benefit to the patient exceeds the possible risk.

Pregnancy and lactation:Bupivacaine Should be used only if the expected benefit for the mother exceeds the possible risk to the fetus.
The use of bupivacaine for paracervical blockade is contraindicated (see section "Contraindications"), since bupivacaine can cause fetal cardiovascular disorders, such as bradycardia / tachycardia.
Bupivacaine has been used in a large number of pregnant women and women of childbearing age, until now there have been no specific changes in reproductive function in women of childbearing age and an increase in the frequency of developmental defects in the fetus.
The addition of epinephrine to bupivacaine can reduce blood flow in the uterus and its contractility, especially when the anesthetic solution is accidentally injected into the mother's vessels.
With intrathecal administration bupivacaine should not be used in the early stages of pregnancy, unless the benefits exceed the risk; in patients with late pregnancy it is recommended to use reduced doses of the drug (see section "Dosing and Administration", "Special instructions").
As well as other local anesthetics, 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 in conducting 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 that the aspiration sample be thoroughly performed before and during the administration of the preparation. If a large dose is required, for example, with epidural blockade, a pre-introduction of the test dose is recommended: 3-5 ml of bupivacaine with epinephrine. The drug is administered slowly at a rate of 25-50 mg / min or fractional, maintaining continuous verbal contact with the patient and controlling the heart rate.With a random intravascular injection of the drug there is a short-term increase in the heart rate, with a random intrathecal injection, a spinal block appears. When signs of intoxication appear, the drug should be discontinued immediately.
Adults and children over 12 years of age
Below are the estimated doses that need to be adjusted depending on the depth of anesthesia and the patient's condition. These doses are considered necessary for successful blockade and should be considered as recommended for the average adult patient.
Dosing recommendations
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, trigeminal blockade of 1-5 ml of the drug (2.5-12.5 mg of bupivacaine) and cervico-thoracic sympathetic node 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.
Large 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 (for example, epidural and caudal anesthesia with natural childbirth): 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).
After 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, 20 ml of the drug are administered at a concentration of 2.5 mg / ml (50 mg of 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 (eg, postoperative boilswhether):

Type of blockade

Concentrations

Scope

Dose

Epidural introduction (at the lumbar level)

Bolus *

Infusion

2,5 mg / ml

5-10 ml

5-7.5 ml / hr

12.5-25 mg

12,5-18,75 mg **

Epidural introduction (at the thoracic level)

Bolus *

Infusion

2,5 mg / ml

5-10 ml

2,5-5 ml / hr

12,5-25 mg

6,25-12.5 mg

Epidural introduction (natural delivery)

Bolus *

Infusion

2,5 mg / ml

6-10 ml

2-5 ml / hr

15-25 mg

5-12,5 mg

* ECwhether during the previous hour the drug was not administered bolus.
** Do not exceed the maximum recommended daily dose (see below).During the surgical intervention, additional administration of the drug is possible.
With simultaneous use of narcotic analgesics dose bupivacaiMr.but it is necessary to reduce it.
With prolonged administration of the drug, the patient should regularly monitor blood pressure, heart rate and other signs of potential toxicity. If toxic effects occur, the drug should be discontinued immediately.
When performing extended blockades from using an extended inf.theor fractionalunitsThe possibility of increasing its concentration in the blood plasma to toxic or the possibility of local damage to nerve fibers should be considered. The experience accumulated to date shows that administration to an adult patient within 24 hours of 400 mg of the drug is usually well tolerated.
For caudal blockade, higher doses of bupivacaineMr.a. Recommended doses if caustic blockade is necessary from higher doses of bupivacaineMr.a. as well as the use of bupivacaiMr.and in ophthalmic surgery are given in the table below.
Bupivacaine with a concentration of 5 mg / ml

Type of blockade	Dose		Start of actionI, minutes	Duration, clock	IndicationsI
Type of blockade	ml	mg	Start of actionI, minutes	Duration, clock	IndicationsI
Retrobulbarnaya	2-4	10-20	5	4-8	Offtalmohirurgy (fromm. section "Special instructions")
Peribulbar	6-10	30-50	10	4-8	Ophthalmic surgery (see section "Special instructions")
Caudal	20-30	100-150	15-30	2-3	Intraoperative and postoperative analgesia. Therapy of pain syndromes and anesthesia in diagnostic procedures (the dose takes into account the test test)

The duration of anesthesia depends on the dose, while the distribution of the drug across segments is difficult to predict, especially when using an isobaric (simple) solution.
When using a large volume of a solution containing ePinephrine, the risk of developing systemic epic effects should be consideredMr.efrina.
Recommended maximum doses
The maximum recommended single dose, calculated at 2 mg / kg body weight, is 150 mg for adults for 4 hours. This is equivalent to 60 ml of the drug at a concentration of 2.5 mg / ml (150 mg buPivacaine) and 30 ml of the 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. In children with high body weight, as a rule, it is necessary to reduce the dose, based on the ideal mass tate. 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 of action, mnn	Duration actions, mines
Acute pain
KaudalynI'm ehpidural 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
ThoracalMr.th epistupidtheanesthesia *	2.5	0,6-0,8	1,5-2	20-30	2-6

*PIn thoracic epidural anesthesia, the drug is injected into thece increasing doses to achieve the desired level of anesthesia.

The dose in children is calculated based on 2 mg per kg of body weight tate.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.Perandtonsusandlar andnfiltrational anesthesia the children from 2 years old: in a dose of 7.5 mg and 12.5 mg per tonsil at a concentration of buPIvacaine 2.5 mg / ml.
Blockade of ilio-inguinal /bydzvezdoshnabout-Pof the nares v 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.Children aged 5 years and over the drug can be administered in a concentration of bupivacaine 5 mg / ml at a dose of 1.25-2 mg / kg.
Blockade of the penis: 0.2-0.5 ml / kg with a bupivacaine concentration of 5 mg / ml, equivalent to 1.0-2.5 mg / kg.Data on epidural anesthesia in children (bolus or continuous administration) are limited.The preparation can be diluted only with compatible solvents, such as 0,9 % solution of sodium chloride, as dilution can change the properties of the drug and lead to the precipitation of bupivacaine. Dilution should be carried out only by qualified personnel with mandatory visual control for mechanical inclusions prior to administration.It is possible to use only clear solutions without visible particles.
The drug solution is intended for single use only.
With intrathecal administration
Dilution of the drug with intrathecal injection (for spinal anesthesia) is not recommended.
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 should reduce the dose.

Indications for use

Concentration,

mg / ml

Dose

Start of action, min

Duration of action, hours

Surgical operations on the lower extremities, including operations on the hip joint

5,0

2-4

10-20

5-8

1,5-4

Recommended injection site - below 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).PIn an unsuccessful attempt, only one additional attempt at introduction at a different level and in a smaller amount should be undertaken. 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.In elderly patients and patients in late pregnancy is recommended to use a reduced dose of the drug.Children with body weight less than 40 kg
Bvapivacaine injection for 5 mg / ml is allowed 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 compared 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 should use the generally accepted guidelines for 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
5-15	0,3-0,4
15-40	0,25-0,3

Side effects:Adverse reactions caused by the drug itself can be difficult to distinguish from the physiological manifestations of nerve blockade (eg, arterial hypotension, bradycardia, temporary urinary retention), reactions caused directly (eg, spinal hematoma) or indirectly (eg, meningitis, epidural abscess) by insertion of a needle or reactions associated with leakage of cerebrospinal fluid (eg, post-puncture headache). The following side effects may develop:
From the immune system:
rarely (> 1/10 000, <1/1000) - allergic reactions, anaphylactic shock.
From the cardiovascular system:
very often (> 1/10) - arterial hypotension,
often (> 1/100, <1/10) - a bradycardia, increase of arterial pressure,
rarely (> 1/10 000, <1/1000) - cardiac arrest, arrhythmia.
From the gastrointestinal tract:
very often (> 1/10) - nausea,
often (> 1/100, <1/10) - vomiting.
From the central nervous system:
often (> 1/100, <1/10) - paresthesia, dizziness,
infrequently (> 1/1000, <1/100) - signs of toxicity from the central nervous system: convulsions, paresthesia around the mouth, numbness of the tongue, hyperacusis, mild dizziness, visual disturbances, loss of consciousness, tremor, noise and ringing in the ears, dysarthria ),
rarely (> 1/10 000, <1/1000) - unintended total spinal block, peripheral nerve damage, paraplegia, paresis, paralysis, neuropathy, arachnoiditis.
From the genitourinary system:
often (> 1/100, <1/10) - urinary retention, incontinence.
From the respiratory system:
rarely (> 1/10 000, <1/1000) - respiratory depression.
On the part of the organs of vision:
rarely (> 1/10 000, <1/1000) is the dip.
When intrathecal administration:
From the immune system:
rarely (> 1/10 000, <1/1000) - allergic reactions, in the most severe cases - anaphylactic shock.
From the cardiovascular system:
very often (> 1/10) - arterial hypotension, bradycardia.
rarely (> 1/10 000, <1/1000) - cardiac arrest.
From the gastrointestinal tract:
very often (> 1/10) - nausea,
often (> 1/100, <1/10) - vomiting.
From the central nervous system:
often (> 1/100, <1/10) - post-puncture headache,
infrequently (> 1/1000, <1/100) - paresthesia, paresis, dies,
rarely (> 1/10 000, <1/1000) - the total spinal block, paraplegia, paralysis, neuropathy, arachnoiditis.
From the genitourinary system:
often (> 1/100, <1/10) - urinary retention, incontinence.
From the musculoskeletal system:
infrequently (> 1/1000, <1/100) - muscle weakness, back pain.
From the respiratory system:
rarely (> 1/10 000, <1/1000) - respiratory depression.
Side effects 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
The use of Bouvanesti® in accordance with the recommendations does not lead to a plasma concentration in which the systemic toxic manifestations may occur. However, when the drug is used in combination with other local anesthetics, acute systemic toxicity can develop through the addition of toxic effects.
Toxic reactions are manifested mainly from the central nervous and cardiovascular systems. These reactions are caused by a high concentration of local anesthetic in the blood, which can result from accidental intravascular injection, overdose or exceptionally high absorption from the high vascularization area (see section "Special instructions").
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. However, the doses commonly used for intrathecal anesthesia do not result in a high systemic concentration of the drug.
Reactions from the central nervous system are similar for all local anesthetics of the amide type, while manifestations from the cardiovascular system are different for different drugs.
A random intravascular injection of a local anesthetic can cause an immediate toxic reaction (within a few seconds-minutes). While overdose signs of systemic toxicity develop later,15-60 minutes after the injection, due to a slow increase in the concentration of the drug in the blood plasma.
From the central nervous system
Intoxication manifests itself gradually in the form of signs and symptoms of impaired function of the central nervous system with an increasing degree of severity. Initial manifestations of intoxication are: paresthesia around the mouth, dizziness, numbness of the tongue, pathologically increased perception of ordinary sounds, tinnitus. Disturbance of vision and tremor are the most serious signs and precede the development of generalized seizures. These phenomena should not be mistakenly regarded as neurotic behavior. Following them, loss of consciousness and the development of large seizures can occur, which can last from a few seconds to several minutes. Due to increased muscular activity and disruption of the normal breathing process, hypoxia and hypercapnia quickly appear after the onset of seizures. In severe cases, breathing may stop. Concomitant acidosis increases the toxic effect of local anesthetics.
These phenomena are due to the redistribution of local anesthetic from the central nervous system and the metabolism of the drug.The described phenomena quickly stop, if the anesthetic was not introduced in excessive amounts.
From the side of the cardiovascular system
Cardiovascular toxicity leads to the most severe consequences and usually precedes the appearance of toxic reactions from the central nervous system that can be masked by general anesthesia or deep sedation with drugs such as benzodiazines or barbiturates.
Due to the high concentration of local anesthetics in blood plasma, arterial hypotension, bradycardia, arrhythmias and, in some cases, cardiac arrest may occur. Toxic reactions from the cardiovascular system are often caused by myocardial depression and myocardial conduction disturbance, which can lead to a decrease in the minute volume of the heart, lowering of arterial pressure, atrioventricular blockade, bradycardia and in some cases to ventricular arrhythmia, including tachycardia and ventricular fibrillation, cardiac arrest . These toxic manifestations often precede the manifestation of symptoms of acute toxicity from the central nervous system, for example, in the form of convulsions,However, in rare cases, cardiac arrest can occur without the appearance of previous signs from the central nervous system.
With a random rapid intravenous bolus injection in the coronary vessels, a high plasma concentration of bupivacaine can be observed, which affects blood circulation and leads to the development of independent cardiotoxic effects or preceded the development of toxic effects from the central nervous system. In this connection, myocardial depression can manifest itself as the first symptoms of intoxication.
When the blockade is performed under general anesthesia in children, the early signs of intoxication are difficult to detect, and careful monitoring is therefore required.
Treatment of acute intoxication
When there are signs of general intoxication or total spinal block, the drug should be stopped immediately and symptomatic therapy of cardiovascular and neurological (seizures, central nervous system) disorders should be performed. In the event of cardiac arrest, cardiopulmonary resuscitation should immediately be used.
Therapy should be aimed at maintaining ventilation, cramping seizures and maintaining 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 seizures occur, therapy should be provided to maintain the cardiovascular system, provide adequate oxygenation and arrest seizures. If necessary, provide oxygen supply and artificial ventilation of the lungs (using an Ambu bag or intubation of the trachea). If convulsions do not stop on their own within 15-20 seconds, then anticonvulsants should be given intravenously: 0.1 mg / kg of diazepam can be used. Prolonged convulsions can interfere with ventilation and oxygenation. In such cases, for rapid arrest of seizures, intubation of the trachea and administration of a muscle relaxant (eg, succinylcholine 1 mg / kg) can be used.
When circulatory insufficiency is introduced dobutamine intravenously, norepinephrine can be administered starting at 0.05 μg / kg / min, if necessary, increase the dose by 0.05 μg / kg / min every 10 minutes. In more severe cases, the dose is titrated according to the results of monitoring hemodynamics.
With obvious inhibition of the cardiovascular system (lowering blood pressure and bradycardia) intravenously administered 5-10 mg of ephedrine, if necessary, after 2-3 minutes, the administration is repeated. Children should be given a dose of ephedrine in accordance with their age and weight.
At a cardiac arrest immediately proceed to cardiopulmonary resuscitation. It is vital to optimize oxygenation and ventilation and support circulation along with correction of acidosis, since hypoxia and acidosis will intensify the systemic toxic effects of the local anesthetic. It should be introduced as soon as possible epinephrine (adrenaline) (0.1-0.2 mg intravenously or intracardiac), if necessary, repeat the introduction. Also, consideration should be given to the need for appropriate therapy with intravenous solutions and the use of fat emulsions.
When cardiac arrest may require prolonged resuscitation.
When choosing a dosing regimen in children, one should take into account the age and body weight.
In the treatment of systemic toxic reactions in children, doses appropriate to the body weight of the child are used.
Special attention should be paid to the early signs of development of intoxication in children, since in this group of patients the most pronounced blockade is most often after the onset of anesthesia.

Interaction:Bupivacaine should be used with caution in patients receiving other local anesthetics or drugs that are similar in structure to local anesthetic agents of the amide type, such as antiarrhythmics (eg, lidocaine, mexiletine), since they can enhance the toxic effects of each other.
Joint use of bupivacaine with antiarrhythmic drugs of class III (eg, amiodarone) has not been studied separately, but caution should be exercised while prescribing these drugs (see also "Special instructions"). Monoamine oxidase inhibitors or tricyclic antidepressants increase the risk of a marked increase in blood pressure. If such simultaneous therapy is necessary, careful monitoring of the patient should be made. Simultaneous use with vasopressor and uterotonic agents (ergot derivatives) can lead to persistentincrease of arterial pressure with possible complications from the cardiovascular and cerebrovascular system.
Combination with total inhalation anesthesia with halothane increases the risk of arrhythmia.
The derivatives of phenothiazine and butyrophenone can reduce or reverse the pressor effect of epinephrine.
When preparing for the introduction, it is necessary to avoid prolonged contact of the drug with metal objects (for example, when treating the injection site of a local anesthetic with disinfectant solutions containing heavy metals), as the risk of local reaction in the form of pain and edema increases. Preparations structurally similar to local anesthetics, for example, toxainide, increase the risk of developing an additive toxic effect.
When combined with drugs that depress the central nervous system, local anesthetics increase the inhibition of the central nervous system. The solubility of bupivacaine decreases at pH> 6.5, this should be taken into account if alkaline solutions are added, since a precipitate can form.
Incompatibility
It is not recommended to mix solutions for intrathecal anesthesia with other drugs.

Special instructions:Regional and intrathecal anesthesia should be performed by experienced specialists in an appropriately equipped room. The equipment and preparations necessary for cardiac monitoring and resuscitation should be available for immediate use. When performing large blockades before the introduction of a local anesthetic, it is recommended to install an intravenous catheter. Personnel conducting anesthesia should undergo appropriate training in the technique of performing anesthesia and should be familiar with the diagnosis and treatment of possible side effects of the drug, systemic toxic reactions and other complications (see section Overdose).
There are reports of cardiac arrest or death during the use of bupivacaine for epidural anesthesia or peripheral blockade. In some cases, resuscitation has been difficult or impossible, despite adequate treatment.
The peripheral nerve blockade is associated with the introduction of a larger volume of local anesthetic into the area of high vascular vascularization,often close to large vessels, where the risk of unintentional intravascular injection of local anesthetic or systemic absorption of a large dose of the drug increases, which in turn 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 its use for local anesthesia leads to a high concentration of the drug in the blood. Most often this is manifested in the case of unintentional intravascular injection or with high vascularization of 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. However, doses commonly used for intrathecal anesthesia, but lead to a high systemic concentration of the drug.
Certain types of blockades, regardless of the local anesthetic used, can be associated with serious adverse reactions, for example:
-Epidural anesthesia, especially against the background of hypovolemia, can lead to inhibition of the cardiovascular system. Care should be taken in patients with cardiovascular disease.
- Large peripheral blockages may require the use of a large amount of local anesthetic in areas of high vascularization, often near large vessels, where the risk of intravascular administration and / or systemic absorption increases, which can lead to a high concentration of the drug in the plasma.
- With retrobulbar injection, the drug can accidentally enter the cranial subarachnoid space, causing temporary blindness, apnea, convulsions, collapse and other side effects. The elimination of these undesirable reactions must be carried out immediately.
- With 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. The severity of these tissue reactions depends on the degree of injury, the concentration of the local anesthetic and the duration of exposure of the tissue with a local anesthetic.Therefore, as with other local anesthetics, the lowest effective concentration and dose of the drug should be used.
Vasoconstrictors can enhance tissue reactions and should be used only on indications.
-If unintentional intravascular injection into the head or neck area, the drug can enter the artery and in this case, even at low doses, the drug is able to cause cerebral symptoms.
-It was reported about cases of chondrolisis with postoperative prolonged intra-articular infusion of local anesthetics. In most of the cases described, infusion into the shoulder joint was performed. Causal relationship with the use of anesthetics is not established. Bupivacaine Do not use for prolonged intra-articular infusion.
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.
When conducting regional anesthesia, you should be especially attentive to the following groups of patients:
-Paients receiving angiaritmic drugs of the III-rd class (for example, amiodarone) should be carefully monitored with continuous monitoring of the ECG, since it is possible to summarize their cardiovascular effects with those of bupivacaine.
-Events of elderly age and patients with severe liver disease, severe renal failure or general unsatisfactory condition.
-Pacients with atrioventricular blockade of II and III degree, since local anesthetics can worsen myocardial conductivity.
-Patients in late pregnancy.
When conducting epidural anesthesia, there may be a drop in blood pressure and a bradycardia. The probability of these complications can be reduced by the preliminary administration of crystalloid and colloidal solutions. With a decrease in blood pressure, immediately introduce sympathomimetics intravenously (eg, 5-10 mg ephedrine); If necessary, their introduction should be repeated.
The drug contains sodium, so in the case of a salt-free diet with a limited intake, the sodium content should be taken into account.
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. The literature describes contradictory data on the mechanism of the onset of this state. Prolonged intra-articular injection is not an approved indication for the use of the drug.
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.
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.
There are cases of arrhythmias, sudden cardiovascular collapse and death. Usually used doses for intrathecal anesthesia do not lead to a high systemic concentration of the drug.
In patients with hypovolemia, regardless of its cause, a sudden severe drop in blood pressure may occur during intrathecal anesthesia. Arterial hypotension, which usually occurs in adults after an intrathecal blockade, is rarely seen in children under the age of 8 years.
Spinal anesthesia can cause intercostal paralysis, and therefore patients with pleural effusion may experience respiratory failure. Septicemia may increase the risk of intraspinal abscess formation during the postoperative period. Possible high or total spinal blockade, disorders of the cardiovascular system in this state, the blockade of the innervation of respiratory muscles and their manifestations.
Neurological complications are a rare consequence of spinal anesthesia and can lead to paresthesia, 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.
Buanavestin® does not contain preservatives, so it should be injected immediately after opening the ampoule. Do not re-sterilize the drug. Remains of the solution must be disposed of.

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.
During the period of application of the drug, one should refrain from driving vehicles and practicing other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

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

Packaging:For 4 ml in ampoules with a capacity of 5 ml or 10 ml or 20 ml in ampoules with a capacity of 10 ml or 20 ml respectively.
For 5 ampoules with a capacity of 5 ml, 10 ml or 20 ml in a contiguous cell pack of a polyvinyl chloride film. 1, 2 contour squares in a pack of cardboard.
For 10 ampoules of 10 ml or 20 ml in a pack of cardboard with corrugated paper partitions.
In each pack insert instruction for use, a knife ampoule or scarifier ampoule (when you pack the ampoules with a break ring, a point and an incision, the ampoule knife or the ampoule scaper does not put it).

Storage conditions:In a dry, protected from light 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 after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002121

Date of registration:03.07.2013 / 04.07.2016

Expiration Date:03.07.2018

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp11.03.2017

Illustrated instructions

Instructions

Buanavestin® (Buvanestin)