Bupivacaine Spinal solution for intrathecal injection 5 mg/ml 4 ml N 5

Pharmacological properties of the drug Bupivacaine

Local anesthetic of the amide group. The action of bupivacaine develops quickly (within 5–10 minutes), the duration of anesthesia is 3–7 hours. The mechanism of action of bupivacaine is due to the stabilization of neuronal membranes and the prevention of the occurrence and conduction of a nerve impulse. When using bupivacaine for caudal or epidural anesthesia, as well as for blockade of peripheral nerves, its maximum concentration in the blood serum is achieved after 30–45 minutes, after which it gradually decreases after 3–6 hours. About 95% of bupivacaine entering the systemic circulation is associated with blood plasma proteins. Bupivacaine (depending on the route of administration) is distributed in various concentrations in the tissues of the body; the maximum concentration is observed in well-perfused tissues (liver, lungs, heart, brain). Penetrates through the placental barrier, however, due to the high degree of binding of the drug to blood plasma proteins, the concentration ratio in the blood of the fetus and mother is low (0.2–0.4). Metabolized mainly in the liver. The half-life in adults is 2.7 hours (1.2-4.6 hours), in children - 6-22 hours. In elderly people, the half-life also increases.

Bupivacaine Spinal solution for intrathecal injection 5 mg/ml 4 ml N 5

Bupivacaine is a local anesthetic drug.

Release form and composition

Bupivacaine is produced in the form of an injection solution: colorless, transparent liquid (4, 10 or 20 ml in clear glass ampoules, 5 ampoules in a strip pack, 1 or 2 packages in a cardboard box; 4 ml in clear glass ampoules, 5 ampoules in a cardboard tray, in a cardboard pack 1 or 2 trays; 4 or 10 ml in ampoules made of polypropylene or low-density polyethylene, in a cardboard pack 5 or 10 ampoules; 20 ml in bottles, 1 or 5 bottles in a cardboard box, 5 bottles in a blister pack, 1 pack in a cardboard box). 1 ml of solution contains: active ingredient: bupivacaine hydrochloride (in the form of bupivacaine hydrochloride monohydrate) – 5 mg; additional components: hydrochloric acid solution or sodium hydroxide solution, sodium chloride, water for injection.

Pharmacological properties

Pharmacodynamics Bupivacaine is a long-acting local anesthetic from the amide group. By preventing the movement of sodium ions through sodium channels, it prevents the conduction of impulses along the nerve fiber; similar effects can be demonstrated in the brain and myocardium. The distinctive features of the drug include the duration of its action, which slightly depends on the combination with epinephrine. Bupivacaine is the drug of choice for continuous epidural anesthesia. At low concentrations, the drug has a shorter duration of effect, and also weakens the effect on motor nerve fibers, which is especially important for short-term pain relief (including in the postoperative period and during childbirth).

Pharmacokinetics The rate of absorption of the drug is affected by the dose, blood supply at the injection site and route of administration. The maximum concentration (Cmax) in plasma during intercostal blockade as a result of rapid absorption is the highest and is 4 mg/l (with the introduction of 400 mg); with subcutaneous injections of the drug into the abdominal area, a lower Cmax is observed. Caudal blockade in children results in rapid absorption and allows high plasma Cmax to be achieved - approximately 1-1.5 mg/L (with an injection of 3 mg/kg body weight). Bupivacaine is characterized by complete two-phase absorption from the epidural space, the half-life (T½) for two phases is 7 minutes and 6 hours, respectively. The volume of distribution (Vd) of the drug at steady state is 73 l, total plasma clearance is 0.58 l/min, hepatic extraction coefficient is 0.4; half-life in blood plasma is 2.7 hours. In newborns, T½ can be longer than in adults and reach up to 8 hours; in children over 3 months it is the same as in adults. The binding of bupivacaine to plasma proteins, mainly alpha-1-acid glycoproteins, is 96%. Following major surgery, levels of this protein may increase and result in higher total plasma concentrations of bupivacaine. At the same time, the free fraction of the drug remains unchanged, as a result of which plasma concentrations exceeding toxic levels are well tolerated. The drug is metabolized almost completely in the liver, through aromatic hydroxylation to 4-hydroxybupivacaine and N-dealkylation to PRA (2,6-pipecoloxylidine), both reactions are catalyzed by the cytochrome CYP3A4 isoenzyme. Clearance is related to hepatic blood flow and the activity of metabolizing enzymes. Slow absorption reduces the rate of elimination of the drug, which is the reason for a longer half-life after intrathecal administration and after injection into the epidural space compared to intravenous administration. When administered intrathecally, bupivacaine is completely absorbed from the subarachnoid space in two phases with T½ - 50–400 minutes, Cmax in plasma is 0.4 mg/l (for every 100 mg).

Indications for use

surgical anesthesia in patients over 12 years of age; acute pain in patients older than 1 year; long-term conduction or epidural anesthesia in cases where significant muscle relaxation should be avoided or the addition of epinephrine is contraindicated; infiltration anesthesia if it is necessary to achieve a long-lasting anesthetic effect (including for postoperative pain); pain relief in obstetrics; spinal anesthesia for surgical interventions on the lower extremities, including operations on the hip joint, with a duration of 3–4 hours and without the need for pronounced motor block - with intrathecal administration.

Contraindications

Absolute: children's age: under 12 years old - for surgical anesthesia, under 1 year old - for all indications for use, with the exception of intrathecal anesthesia (with this method, Bupivacaine can be used from birth); severe arterial hypotension (hypovolemic/cardiogenic shock); intravenous regional anesthesia (Bir block) (since acute systemic toxic reactions may occur as a result of accidental penetration of the drug into the bloodstream); paracervical blockade in obstetrics; hypersensitivity to any of the components of the drug or to other amide-type local anesthetics. Contraindications to epidural/intrathecal anesthesia are: hypovolemic/cardiogenic shock; purulent infectious skin lesions at or near the site of lumbar puncture; meningitis, polio, intracranial hemorrhage, tumors and other diseases of the central nervous system (CNS); tumors, spondylitis, tuberculosis and other active diseases or injuries of the spine (including fractures); spinal stenosis; sepsis, subacute combined degeneration of the spinal cord caused by pernicious anemia and brain/spinal cord tumors; bleeding disorder or concomitant anticoagulant therapy. Relative (bupivacaine is used with caution in the following diseases/conditions): heart block (possibly impaired intracardiac patency); cardiovascular failure (due to risk of progression); renal failure; decreased blood flow in the liver (including against the background of liver disease, chronic heart failure); general serious condition; cholinesterase deficiency; age from 1 year to 12 years and over 65 years; III trimester of pregnancy; diseases of an inflammatory nature or infection of the injection site (with infiltration anesthesia); simultaneous use with antiarrhythmic drugs (including beta-blockers), local anesthetics or agents that have a similar structure to amide-type anesthetics, for example, mexiletine or lidocaine.

Directions for use and dosage

The use of the drug is possible only by doctors experienced in local anesthesia, or under their supervision. Administration of the drug must be carried out in rooms equipped with equipment designed for immediate resuscitation measures. To achieve the required degree of anesthesia, the minimum possible dose of anesthetic should be used. Intravascular administration of Bupivacaine is prohibited. Before using the drug and during its use, it is recommended to carry out an aspiration test. Administration must be carried out slowly, at a rate of 25–50 mg/min or fractionally, maintaining constant verbal contact with the patient while periodically monitoring the heart rate. When performing epidural anesthesia, a dose of 3–5 ml of bupivacaine in combination with epinephrine should be administered first. Accidental intravascular administration may cause a short-term increase in heart rate, and accidental intrathecal administration may cause spinal block. Immediate systemic toxic reactions due to unintentional intravascular administration of the drug may develop within a few seconds/minutes after injection. If signs of toxicity occur, administration should be stopped immediately. Recommended indicative doses that need to be adjusted taking into account the patient’s condition and the required depth of anesthesia: therapeutic and diagnostic blockade: bupivacaine concentration 2.5 mg/ml – 2.5–100 mg, for example, with blockade of the cervicothoracic ganglion of the sympathetic trunk – 25– 50 mg, trigeminal nerve – 2.5–12.5 mg; infiltration anesthesia: concentration 2.5 mg/ml – 12.5–150 mg; concentration 5 mg/ml – 25–150 mg; major blockades (including epidural blockade, sacral/brachial plexus blockade): concentration 5 mg/ml – 75–150 mg; intercostal blockade: concentration 5 mg/ml – 10–15 mg per nerve, but not more than 10 nerves; epidural analgesia in the form of intermittent bolus administration: concentration 2.5 mg/ml - initial dose of 50 mg, then every 4-6 hours, depending on the age of the patient and the number of damaged segments, 15-40 mg; epidural anesthesia for cesarean section: concentration 5 mg/ml – 75–150 mg; anesthesia in obstetrics (including caudal and epidural anesthesia during natural childbirth): concentration 2.5 mg/ml - 15-25 mg, 5 mg/ml - 30-50 mg, repeated administration is possible every 2-3 hours at the initial dose. Recommended volumes of solution for epidural administration as a continuous infusion, including against the background of postoperative pain with the following types of blockade (drug concentration 2.5 mg/ml): natural birth: for infusion 2–5 ml/h, for bolus* – 6–10 ml; lumbar level: for infusion 5–7.5 ml/hour, for bolus* – 5–10 ml; thoracic level: for infusion 2.5–5 ml/hour, for bolus* – 5–10 ml. *Administered in cases where the drug was not administered as a bolus during the previous hour. During surgery, additional use of the solution is allowed. When used in combination with narcotic analgesics, the dose of the drug should be reduced. In the case of prolonged administration of Bupivacaine, it is necessary to regularly monitor heart rate, blood pressure and other indicators that indicate possible symptoms of intoxication, if detected, the administration of the solution is immediately stopped. The recommended maximum single dose for adults and children 1–12 years of age is based on the calculation of 2 mg per 1 kg of body weight. For adults, it is 150 mg of bupivacaine over 4 hours (2.5 mg/ml concentration - 60 ml, 5 mg/ml concentration - 30 ml). The recommended maximum dose per day is 400 mg (adjusted depending on the physique, age of the patient and other significant conditions). As a rule, in children with high body weight, the dose is reduced based on the ideal body weight. Children need to administer the solution slowly, dividing the total dose into several injections (especially when performing thoracic/lumbar epidural anesthesia), while continuously monitoring vital signs. When performing thoracic, lumbar and caudal epidural anesthesia in children, a solution with a concentration of 2.5 mg/ml is prescribed at an approximate dose of 1.5–2 mg/kg (volume 0.6–0.8 ml/kg). For thoracic epidural anesthesia, bupivacaine is administered in increasing doses until the required level of analgesia is achieved. When performing regional blockade (for example, blockade and infiltration of small nerves) and peripheral nerve blockade (for example, blockade of the iliohypogastric/ilioinguinal nerves), a solution with a concentration of 2.5 or 5 mg/ml is administered at an estimated dose of 0.5–2 mg /kg. Recommended doses of Bupivacaine in children for other indications: blockade of the iliohypogastric and ilioinguinal nerves in children over 1 year of age: concentration 2.5 mg/ml - 0.1–0.5 ml/kg (corresponding to 0.25–1. 25 mg/kg); over the age of 5 years, the drug can be used at a concentration of 5 mg/ml; Penile blockade: concentration 5 mg/ml – 0.2–0.5 ml/kg (corresponding to 1–2.5 mg/kg); peritonsillar infiltration anesthesia in children over 2 years of age: concentration 2.5 mg/ml - 7.5 and 12.5 mg per tonsil. Information on the administration of epidural anesthesia in children (continuous or bolus administration) is limited. For intrathecal administration of Bupivacaine, the dose is selected individually. In the case of surgical interventions on the lower extremities (including operations on the hip joint), adults are prescribed a dose of 10–20 mg (2–4 ml) for intrathecal administration. The drug begins to act 5–8 minutes after administration; the duration of anesthesia can vary from 1.5 to 4 hours. The recommended injection site is at the level of L3 (third lumbar vertebra). Before injection, intravenous access must be provided. There is no experience with doses exceeding 20 mg. The solution can be administered only after confirmation of its entry into the subarachnoid space. The lack of effect may be due to poor distribution of the substance in the subarachnoid space; this disorder can be corrected by changing the position of the patient. Children weighing less than 40 kg are allowed to use a solution at a concentration of 5 mg/ml. Due to the fact that the volume of cerebrospinal fluid in newborns and infants is larger, they require a relatively high dose per 1 kg of body weight to achieve the same degree of blockade as adults, in comparison with the latter. Recommended guideline doses for children weighing up to 40 kg: weight 15–40 kg: 0.25–0.3 mg/kg; weight 5–15 kg – 0.3–0.4 mg/kg; weight less than 5 kg – 0.4–0.5 mg/kg. The solution is for single use only. To obtain a solution of Bupivacaine at a concentration of 2.5 mg/ml, a drug with a concentration of 5 mg/ml can be diluted with 0.9% sodium chloride solution for injection.

Side effects

nervous system: often – dizziness, paresthesia; uncommon – symptoms of central nervous system toxicity (perioral paresthesia, convulsions, hyperacusis, numbness of the tongue, tremor, loss of consciousness, tinnitus, mild dizziness, dysarthria, visual impairment); rarely - arachnoiditis, paraplegia, paresis, neuropathy, damage to peripheral nerves; cardiovascular system: very often – decreased blood pressure (BP); often – increased blood pressure, bradycardia; rarely - arrhythmia, cardiac arrest; digestive tract: very often – nausea; often - vomiting; immune system: rarely - anaphylactic shock, allergic reactions; organ of vision: rarely – diplopia; urinary system: often – urinary retention; organs of the mediastinum and chest, respiratory system: rarely - respiratory depression. Side effects noted with intrathecal administration of Bupivacaine: nervous system: often - headache that appears after puncture of the dura mater; uncommon – dysesthesia, paresis, paresthesia; rarely - paraplegia, complete unintentional spinal block, arachnoiditis, neuropathy, paralysis; immune system: rarely - anaphylactic shock, allergic reactions; urinary system: often – urinary retention/incontinence; respiratory organs: rarely - respiratory depression; cardiovascular system: very often – bradycardia, decreased blood pressure; rarely - cardiac arrest; digestive tract: very often – nausea; often - vomiting; musculoskeletal system: uncommon – back pain, muscle weakness. Adverse effects caused by bupivacaine are difficult to distinguish from physiological reactions resulting from nerve blockade and events caused (directly or indirectly) by drug administration or cerebrospinal fluid leakage. In children, adverse reactions of therapy are similar to those in adults, but early symptoms of toxic reactions of the drug in them are more difficult to determine if the blockade is carried out under anesthesia or sedation.

Overdose

Bupivacaine can cause acute toxic reactions in the cardiovascular and central nervous systems associated with a significant increase in its level in the blood. Such disorders appear mainly as a result of accidental intravascular administration, overdose, or excessively rapid absorption of the drug from highly vascularized tissues. Symptoms of systemic toxicity in case of overdose due to a slow increase in drug concentration in the blood are observed 15–60 minutes after injection. Signs of central nervous system intoxication appear gradually; generalized convulsions are usually preceded by less severe symptoms (see section “Side effects”). These effects should not be misinterpreted as a neurotic disorder; they may be followed by loss of consciousness and a grand mal seizure lasting several seconds/minutes. During convulsions, hypercapnia and hypoxia intensify; in severe cases, respiratory arrest is possible. Acidosis aggravates the toxic effects of the drug. Resolution of the above symptoms occurs as a result of the metabolism of the drug and its redistribution from the central nervous system, subject to a slight overdose. Adverse cardiovascular effects are usually preceded by signs of CNS toxicity, which may be masked by deep sedation or anesthesia. Conduction disturbances and myocardial depression lead to arterial hypotension, decreased cardiac output, development of AV block (atrioventricular block), bradycardia, ventricular arrhythmia (including ventricular tachycardia and ventricular fibrillation) and cardiac arrest. These lesions are usually preceded by signs of severe CNS toxicity, but in rare cases cardiac arrest has occurred in their absence. When blood pressure decreases and/or bradycardia occurs, administration of a vasopressor with an inotropic effect is required. If symptoms of acute systemic intoxication develop, the administration of bupivacaine should be stopped immediately and measures should be taken to maintain circulation, ensure adequate ventilation and oxygenation, and, if necessary, resort to intubation. In case of seizures, diazepam is prescribed, in case of bradycardia - atropine, in case of circulatory failure - intravenous injections of dobutamine, it is possible to administer norepinephrine at an initial dose of 0.05 mcg/kg per minute, followed by increasing the dose every 10 minutes by 0.05 mcg/kg per minute (in more serious cases, the dose is titrated). The administration of ephedrine is allowed, and acidosis is also corrected. Special instructions With some types of local anesthesia, the following serious disorders may develop: accidental intravascular injection into the neck/head area: cerebral symptoms may develop; peribulbar and retrobulbar administration: development of persistent dysfunction of the eye muscles (due to injury and/or local toxic effects); retrobulbar administration: the appearance of apnea, temporary blindness, convulsions, collapse and other undesirable effects (due to penetration of the drug in rare cases into the subarachnoid space); immediate relief of these symptoms is necessary; epidural anesthesia: depression of cardiovascular function (especially with concomitant hypovolemia); Caution is required when using the drug in patients with lesions of the cardiovascular system. To reduce the likelihood of bradycardia and a decrease in blood pressure occurring during epidural anesthesia, crystalloid and colloid solutions should be pre-administered. When blood pressure decreases, immediate intravenous injections of sympathomimetics (including ephedrine at a dose of 5–10 mg) are administered. Due to the potential for chondrolysis, long-term intra-articular administration of Bupivacaine is not an approved indication for its use. Spinal anesthesia can cause severe blockade and paralysis of the intercostal muscles and diaphragm. In rare cases, an adverse reaction to spinal anesthesia may be the appearance of high/complete spinal blockade, leading to respiratory and cardiovascular depression. Sometimes the consequences of spinal anesthesia may include neurological complications, causing disorders such as muscle weakness, paresthesia, anesthesia, paralysis (rarely they can be permanent). Before prescribing treatment, it is necessary to weigh the expected benefits and possible risks in patients suffering from paraplegia, neuromuscular disorders, multiple sclerosis and hemiplegia. After opening the bottle/ampoule, the solution must be administered immediately, since it contains no preservatives.

Impact on the ability to drive vehicles and complex mechanisms

When driving vehicles and operating complex mechanisms, it should be taken into account that the drug may have a temporary effect on coordination of movements, as well as motor function. Use during pregnancy and lactation The use of Bupivacaine for paracervical block anesthesia in obstetrics is contraindicated, as it can cause severe disturbances in the fetus in the form of bradycardia or tachycardia. For other indications, the use of the drug is allowed only if the expected benefit to the mother significantly outweighs the possible threat to the health of the fetus. When administered intrathecally in late pregnancy, the dose of the drug should be reduced due to the increased risk of high/complete spinal block. Bupivacaine can pass into breast milk, but when used in therapeutic doses, the risk of affecting the baby is minimal.

Use in childhood

Due to the fact that the safety profile of the drug in children under 1 year of age has not been thoroughly studied, the use of bupivacaine in this group of patients is prohibited, except for intrathecal anesthesia - in this case, the drug can be used from the day of birth. During surgical anesthesia, Bupivacaine is contraindicated for use in children under 12 years of age. There are no data on intra-articular blockade and blockade of large nerves with an anesthetic in children from 1 to 12 years of age. When performing epidural anesthesia, the drug must be administered slowly, taking into account the body weight and age of the child, since, especially with epidural anesthesia at chest level, severe hypotension and respiratory distress may occur. In case of impaired renal function, the drug should be used with caution in the presence of renal failure. In case of liver dysfunction, the drug should be prescribed with caution in case of liver diseases accompanied by a decrease in hepatic blood flow. Use in the Elderly Bupivacaine should be used with caution in patients over 65 years of age. When administered intrathecally, elderly patients require a reduction in the recommended dose, due to the existing likelihood of high/complete spinal block.

Drug interactions

class Ib antiarrhythmic drugs, other local anesthetics: an additive effect of their toxic interaction with bupivacaine is noted; class III antiarrhythmic drugs (amiodarone, etc.): possible aggravation of toxic cardiovascular reactions. Since metal ions can lead to the development of a reaction in the form of swelling and pain at the injection site of bupivacaine, during preparation for administration it is necessary to avoid prolonged contact of the drug with metal objects. Analogs Analogs of Bupivacaine are: Bupivacaine hydrochloride, Bupivacaine Grindeks, Bupivacaine-Binergia, Marcaine Spinal, Bupivacaine-Grindeks Spinal, Bupivacaine-M, Buvanestin, Marcaine, Omnicaine, Anecaine, Carbostezin, Bupicaine, Marcaine Spinal Heavy, Maxicaine, Sensorcaine, BlokkoS.

Terms and conditions of storage

Store out of reach of children, protected from light, at a temperature not exceeding 25 °C, without freezing

Shelf life – 3 years.

Conditions for dispensing from pharmacies Dispensed by prescription.

Use of the drug Bupivacaine

The dose of bupivacaine depends on the type of pain relief. Typically, for epidural anesthesia, adults weighing up to 70 kg are administered in a single dose of 50-100 mg, for caudal anesthesia - 75-150 mg, for peripheral nerve blockade - 25-150 mg. A single dose of bupivacaine should not exceed 150–175 mg (2 mg per 1 kg of body weight). Repeated use of bupivacaine is possible after 3–6 hours, and the daily dose should not exceed 400 mg. Bupivacaine is administered slowly with repeated aspiration to avoid intra-articular administration at the minimum effective dose.

BUPIVACAIN

Directions for use and doses

Bupivacaine should only be administered by physicians experienced in administering local anesthesia or under their supervision.
To achieve the required degree of anesthesia, the minimum possible dose must be administered. Under no circumstances should accidental intravascular administration of the drug be allowed. Before and during administration of the drug, it is recommended to carry out an aspiration test. The drug must be administered slowly, at a rate of 25-50 mg/min or in fractions, maintaining continuous verbal contact with the patient and monitoring the heart rate. During epidural administration, a dose of 3-5 ml of bupivacaine with epinephrine is pre-administered. With accidental intravascular administration, a short-term increase in heart rate occurs; with accidental intrathecal administration, a spinal block occurs. If toxic signs occur, administration is stopped immediately.

Below are approximate doses that need to be adjusted 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 bupivacaine) and
cervicothoracic ganglion sympathetic trunk
10-20 ml of the drug (25-50 mg bupivacaine).

Intercostal blockade

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

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

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

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

Epidural anesthesia for caesarean section:

15-30 ml of the drug at a concentration of 5 mg/ml (75-150 mg bupivacaine).

Epidural analgesia as an intermittent bolus:

Initially, 20 ml of the drug is administered at a concentration of 2.5 mg/ml (50 mg bupivacaine), then every 4-6 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 bupivacaine).

Epidural analgesia as a continuous infusion

(for example, post-operative pain):

1If the drug was not administered as a bolus within the previous hour.

2 The maximum recommended daily dose should not be exceeded (see below).

During surgery, additional administration of the drug is possible.

When using narcotic analgesics simultaneously, the dose of bupivacaine should be reduced.

During long-term administration of the drug, the patient should be regularly monitored for blood pressure, heart rate, and other signs of potential toxicity. If toxic effects occur, administration of the drug must be stopped immediately.

During surgery, additional administration of the drug is possible.

When using narcotic analgesics simultaneously, the dose of bupivacaine should be reduced.

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

Maximum recommended doses

The maximum recommended single dose, calculated at 2 mg/kg body weight, is 150 mg over four hours for adults. 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 relevant conditions.

Children aged 1-12 years

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

The dosages for children given in the table are approximate. There may be variability. In children with high body weight, it is usually necessary to reduce the dose based on ideal body weight. Generally accepted anesthesia guidelines should be used when determining anesthesia techniques and taking into account individual patient characteristics.

The minimum dose necessary to achieve sufficient anesthesia should be administered.

a) the onset and duration of peripheral nerve block depends on the nature of the block and the dose

b) for thoracic epidural anesthesia, the drug is administered in increasing doses until the desired level of pain relief is achieved.

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, an 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 during lumbar and thoracic epidural anesthesia, while continuously monitoring vital signs.

Peritonsillar infiltration anesthesia in children from 2 years of age

: at a dose of 7.5 mg and 12.5 mg per tonsil at a bupivacaine concentration of 2.5 mg/ml.

Blockade of the ilioinguinal/iliohypogastric nerves in children from 1 year of age:

0.1-0.5 ml/kg at a bupivacaine concentration of 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 at a bupivacaine concentration of 5 mg/ml, which is equivalent to 1.25-2 mg/kg.

Penis block:

0.2-0.5 ml/kg at a bupivacaine concentration of 5 mg/ml, which is equivalent to 1.0-2.5 mg/kg.

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

Cooking method

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

The drug solution is intended for single use only.

With intrathecal administration

Bupivacaine should only be administered by physicians experienced in administering local anesthesia or under their supervision. To achieve the required degree of anesthesia, the minimum possible dose must be administered.

The doses given below are for adults. Dose selection is carried out individually.

Elderly patients

and
for patients in late pregnancy,
the dose should be reduced.

The recommended injection site is at the L3 level.

There is no clinical experience with doses exceeding 20 mg. Before administering the drug, intravenous access must be provided.

Administration is carried out only after confirmation of entry into the subarachnoid space (outflow of clear cerebrospinal fluid from the needle or during aspiration). If the attempt is unsuccessful, only one additional attempt at administration should be made at a different level and in a smaller volume. One of the reasons for the lack of effect may be poor distribution of the drug in the subarachnoid space, which can be corrected by changing the position of the patient.

Children weighing less than 40 kg

Bupivacaine, solution for injection, 5 mg/ml, can be used in children.

The main difference between adults and children is that newborns and infants have a larger volume of cerebrospinal fluid, which requires a relatively higher dose per kilogram of body weight to achieve the same degree of block compared to adults.

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

The dosages for children given in the table are approximate. There may be variability. Generally accepted anesthesia guidelines should be used when determining anesthesia techniques and taking into account individual patient characteristics. The minimum dose necessary to achieve sufficient anesthesia should be administered.

Side effects of the drug Bupivacaine

Most often occur due to high serum concentrations of bupivacaine due to overdose, accidental intravascular administration, or impaired metabolism. Possible agitation, anxiety, dizziness, ringing in the ears, blurred vision, tremor, convulsions, depression, drowsiness, coma, respiratory arrest, nausea, vomiting, chills, miosis, inhibition of myocardial contractility with a decrease in cardiac output, conduction disorders, arterial hypotension, bradycardia, ventricular arrhythmia (ventricular tachycardia, ventricular fibrillation), asystole, rarely - allergic reactions (urticaria, itching, erythema, angioedema, including laryngeal edema, tachycardia, sneezing, sweating, drug fever) up to anaphylactic shock. Side effects after epidural and caudal anesthesia can be temporary or permanent: spinal block with hypotension, urinary retention, fecal and urinary incontinence, loss of perineal sensation and impaired sexual function, persistent anesthesia, paresthesia, weakness and paralysis of the lower extremities, headache and pain in the lower extremities. sacral area, meningism, septic meningitis, delayed labor.

Bupivacaine

Acute systemic toxicity

Symptoms

Symptoms of acute systemic toxicity may occur in the central nervous system and cardiovascular system. They are caused by high concentrations of local anesthetic in the blood as a result of accidental intravascular administration of the drug, overdose, or unusually rapid absorption from an area of ​​high vascularity (see section “Special Instructions”).

Symptoms of CNS toxicity are similar for all amide-type local anesthetics, while cardiovascular manifestations vary more widely between drugs. Accidental intravascular administration of a local anesthetic may cause immediate (seconds to minutes) systemic toxicity. In case of overdose, symptoms of systemic toxicity develop later (15-60 minutes after injection) due to a slower increase in the concentration of local anesthetic in the blood.

Manifestations of CNS toxicity develop gradually in the form of signs and symptoms of CNS dysfunction, the severity of which increases. Initial manifestations of toxicity usually include dizziness, perioral paresthesia, numbness of the tongue, hyperacusis, tinnitus and visual disturbances. Dysarthria, muscle twitching, or tremors are more serious symptoms and precede the development of generalized seizures. These phenomena should not be mistakenly regarded as neurotic behavior. They may be followed by loss of consciousness and the development of large convulsive seizures lasting from several seconds to several minutes. Due to increased muscle activity and disruption of the normal breathing process, hypoxia and hypercapnia appear soon after the onset of convulsions. In severe cases, apnea may develop. Acidosis enhances the toxic effect of local anesthetics. These phenomena are resolved due to the metabolism of the local anesthetic and its redistribution from the central nervous system. Relief of toxic effects can occur quickly if the anesthetic was not administered in very large quantities.

The appearance of symptoms of toxicity from the cardiovascular system, as a rule, indicates the severity of the clinical situation. They are usually preceded by symptoms of central nervous system toxicity, which may be difficult to recognize during general anesthesia or deep sedation with drugs such as benzodiazepines and barbiturates. Against the background of high systemic concentrations of local anesthetics, arterial hypotension, bradycardia, arrhythmia and, in some cases, cardiac arrest were noted. Toxic reactions from the cardiovascular system are often associated with impaired intracardiac conduction and myocardial function, which leads to a decrease in cardiac output, arterial hypotension, atrioventricular block, bradycardia and, in some cases, to ventricular arrhythmia, including ventricular tachycardia, ventricular fibrillation and cardiac arrest. These symptoms are usually preceded by severe CNS toxicity such as seizures, but in rare cases cardiac arrest has occurred without preceding CNS symptoms. With very rapid intravenous bolus administration, high concentrations of bupivacaine can be achieved in the coronary arteries, and cardiovascular toxic effects may occur without or precede CNS symptoms. In such cases, myocardial depression may be the first symptom of toxicity.

Particular attention should be paid to identifying early signs of systemic toxicity in children, since extensive blocks are often performed under general anesthesia.

Treatment

In the case of a complete spinal block, adequate ventilation should be ensured (maintenance of the airway, oxygen supply, and, if necessary, intubation and artificial ventilation of the lungs). For hypotension/bradycardia, vasopressors are administered, preferably with a positive inotropic effect.

If symptoms of acute systemic toxicity occur, local anesthetic administration should be discontinued immediately. Treatment should be aimed at maintaining adequate ventilation (with oxygen) and hemodynamics.

In all cases of systemic toxicity, oxygen therapy is necessary. If necessary, intubation and artificial ventilation (possibly with hyperventilation) should be used. For convulsions, administration of diazepam is indicated, for bradycardia - atropine.

With the development of vascular shock (arterial hypotension, bradycardia), therapy includes intravenous administration of infusion solutions, vasopressors, inotropic drugs and/or fat emulsions. Intravenous infusion solutions, dobutamine, and, if necessary, norepinephrine should be administered (initially at a dose of 0.05 mcg/kg/min., and, if necessary, increase the dose by 0.05 mcg/kg/min. every 10 minutes), guided by monitoring data of hemodynamic parameters in more severe cases. Ephedrine can also be used. If blood circulation stops, long-term (several hours) resuscitation measures may be required. In all cases, acidosis must be corrected. When treating acute toxicity in children, their age and body weight should be taken into account when choosing drug doses.

Special instructions for the use of the drug Bupivacaine

The dose for elderly people and patients with mental retardation, as well as for patients with arterial hypotension, heart block and circulatory failure should be selected individually, taking into account physical status. Since amide anesthetics are metabolized in the liver, caution is required when prescribing bupivacaine to patients with hepatic or renal impairment. Bupivacaine should only be used during pregnancy if absolutely necessary. It is not recommended to use bupivacaine during breastfeeding. During anesthesia, blood pressure, heart rate and respiration should be monitored. Before starting anesthesia, it is necessary to prepare resuscitation equipment and a set of medications to eliminate anaphylaxis, as well as create conditions to facilitate emergency treatment of conditions caused by possible systemic toxicity of the anesthetic.

Bupivacaine (Bupivacainum)

For epidural anesthesia, only single-use vials are used; the solution does not contain antimicrobial additives. Do not use solutions containing antimicrobial agents (chlorobutanol, methylparaben).

When performing epidural anesthesia, it is necessary to carry out a test dose with 3-5 ml of anesthetic. During the test dose, verbal contact is maintained with the patient for 5 minutes and the heart rate is regularly determined. Aspiration is carried out before the main dose is administered, which is administered slowly, under constant monitoring. When minimal toxic effects occur, administration is stopped.

There is also insufficient data on the effectiveness and safety of the use of bupivacaine for paracervical anesthesia in other cases.

A 0.25% bupivacaine solution usually does not provide complete motor blockade; it is used in situations where complete muscle relaxation is not necessary. However, in some patients, a 0.25% solution causes complete motor blockade of the intercostal nerves, which can be used during surgical interventions on the abdominal organs.

A 0.5% solution of bupivacaine provides motor blockade and a certain degree of muscle relaxation during caudal, epidural or conduction anesthesia; with long-term infusion through a catheter, repeated injections increase the severity of motor blockade; in some cases, with the first administration of a 0.5% solution, complete motor blockade is achieved.

A 0.75% solution of bupivacaine provides complete motor blockade and complete muscle relaxation; when used for epidural anesthesia, a single injection is recommended; should not be administered by continuous infusion.

The use of bupivacaine 0.75% for epidural anesthesia in obstetrics is not recommended because inadvertent intravascular administration may result in cardiac arrest in the mother; solutions of lower concentrations can be used. It is necessary to administer the minimum dose that provides safe and adequate pain relief without toxic effects, prolonged hypotension, or decreased muscle strength. In most cases in obstetrics, it is possible to achieve analgesia with a long-term infusion of 0.0625-0.125% bupivacaine solution at a rate of 10-15 ml per hour. Concomitant epidural administration of fentanyl (1-2 mcg/ml) or sufentanil (0.1-0.2 mcg/ml) can reduce the concentration or rate of infusion of bupivacaine during epidural anesthesia. Using the lowest effective dose reduces the risk of maternal and fetal toxicity, but in some cases higher concentrations are used to control blood pressure or eliminate the sensation of muscle contractions.

It is necessary to weigh the potential risks and benefits of using bupivacaine when there is a decrease in hepatic blood flow (chronic heart failure, liver or kidney disease or dysfunction), since this reduces the clearance of the drug, increases the risk of toxicity and it may be necessary to reduce the dose and/or increase the interval between doses; in case of cardiac conduction disorders, shock, hypotension, hypovolemia, since it is possible to suppress myocardial functions and aggravate these disorders; in case of inflammation and/or infections in the area of ​​the intended injection or application, since a change in the local pH is possible with a decrease or absence of the effect of local anesthetics; in case of kidney pathology, since the anesthetic or its metabolites can accumulate; in very young or old age, with acute pathology, in weakened patients, since sensitivity to the toxic effects of local anesthetics is increased; with plasma cholinesterase deficiency and in children under 12 years of age.

It is necessary to weigh the potential risks and benefits of using bupivacaine for epidural (caudal or lumbar epidural) anesthesia in patients with neurological pathology and sepsis, since hyperstimulation of the central nervous system is possible, as well as in spinal deformities that can affect the technique of administration or the effect of local anesthetics.

It is necessary to weigh the potential risks and benefits of using bupivacaine for subarachnoid anesthesia in patients with chronic back pain, since exacerbation is possible; for infectious, tumor, and other pathologies of the central nervous system; for coagulation disorders due to anticoagulant therapy or hematological diseases, since damage to blood vessels during anesthesia can lead to uncontrolled hemorrhage into the central nervous system or soft tissues; in patients with a history of headache or migraine, since its aggravation or exacerbation is possible; when blood is detected in the cerebrospinal fluid, since there is a high probability of unintentional intravascular injection; for hypertension and hypotension, since they may be aggravated by cardiac dysfunction or vasodilation; with paresthesia, psychosis, hysteria or lack of contact with the patient; for spinal deformities that affect the technique of administration and/or the effect of local anesthetics; with subarachnoid hemorrhage.

It is necessary to weigh the potential risks and benefits of using bupivacaine in combination with vasoconstrictors for bronchial asthma, as the risk of anaphylactoid reactions or bronchospasm induced by sulfites in the combination drugs increases; for heart disease, heart rhythm disturbances, diabetes; with hyperthyroidism, since there is increased sensitivity to the cardiac stimulating effect of vasoconstrictors; in diseases of peripheral vessels, since additional vasoconstriction increases the likelihood of severe hypertension, ischemia, and necrosis.

In children under 9 months of age, plasma alpha1-acid glycoprotein concentrations are usually low and unbound plasma bupivacaine is elevated, increasing its toxicity; in newborns, the total clearance of bupivacaine is up to 1/3-1/2 of that for adults, which also increases the toxicity of the drug. In the United States, bupivacaine is approved for use in children over 12 years of age.

Impact on the ability to drive vehicles and machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose of the drug Bupivacaine

Symptoms of acute overdose occur when the concentration of bupivacaine in the blood serum increases, most often with accidental intravascular, intraarticular or subarachnoid administration and are manifested by systemic toxic effects. Emergency measures - ensuring airway patency followed by mechanical ventilation to prevent apnea, catheterization of a vein; when collapse develops, an infusion of vasopressor drugs is administered, and when seizures occur, anticonvulsant therapy is administered.

List of pharmacies where you can buy Bupivacaine:

• Moscow
• Saint Petersburg