Overview
Pharmacokinetics
Systemic absorption depends on the method of administration, vascularization of the area of administration. Bupivacaine is completely absorbed from the subarachnoid and epidural spaces; absorption is biphasic. TCmax during caudal epidural and conduction anesthesia - 30-40 minutes. Cmax during spinal anesthesia at a dose of 20 mg - 0.1 μg / ml. The total clearance from plasma is 580 ml / min, the volume of best is 73 l, T1 / 2 is 3.5 hours, the rate of hepatic extraction is 0.4. Communication with including proteins (mainly with alpha1-glycoprotein) is 96%. During intercostal blockades (due to rapid absorption), the highest plasma concentrations of the drug are determined (1-4 mg / l after administration of a total dose of 400 mg), while after s / c administration to the region of the anterior abdominal wall, it creates the lowest concentration in plasma. Another medical children, rapid absorption and a high concentration of the drug in plasma (1-1.5 mg / l, administered dose of 3 mg / kg) are observed with caudal blockade. In newborns, T1 / 2 is 8.1-14 hours. In children older than 3 months, T1 / 2 is the same as in adults. An increase in the concentration of alpha-1-glycoprotein in the postoperative period can lead to an increase in the total concentration of bupivacaine in the plasma, while the concentration of the unbound fraction does not change, and the total plasma concentration exceeding the toxic (2.3-3 mg / L) is well tolerated. Penetrates through the placenta. The connection with plasma proteins in the fetus is lower than in the mother, the concentration of the unbound fraction in the fetus and mother is the same. Secreted with mother's milk. It is metabolized (the main metabolite is 2,6-pipecoloxylidine), excreted mainly by the kidneys, only 5% of bupivacaine is excreted unchanged in the urine. After epidural administration, about 0.2% of unchanged bupivacaine, 1% pipecoloxylidine, and about 0.1% 4-hydroxybupivacaine are found in the urine.
Indications
Various types of local anesthesia (pain relief during trauma, surgical interventions, including cesarean section, labor pain relief, painful diagnostic procedures, such as arthroscopy):
local infiltration anesthesia (including in dentistry),
conduction anesthesia (including in dentistry, intercostal block, cervical vagosympathetic, block of large and small nerves),
caudal or lumbar epidural block,
spinal (subarachnoid) anesthesia,
retrobulbar (regional) anesthesia.
Contraindications
Hypersensitivity (including to other amide local anesthetizing drugs). It is not used for intravenous regional anesthesia (Beer blockade) (accidental penetration of bupivacaine into the bloodstream can cause the development of acute systemic toxic reactions), it is not used for paracervical blockade for anesthesia during childbirth (it can cause fetal death), children up to 5 years. General contraindications for epidural anesthesia: acute diseases of the central nervous system, severe arterial hypotension (cardiogenic or hypovolemic shock), pustular skin lesion at the site of the proposed puncture. General contraindications for intrathecal anesthesia: acute diseases of the central nervous system, such as meningitis, poliomyelitis, intracranial hemorrhage, as well as neoplasms of the central nervous system; narrowing of the spinal canal and diseases of the spine in the acute phase (spondylitis, tumor) or recent trauma (fracture) of the spine; sepsis; pernicious anemia with subacute combined degeneration of the spinal natural pustular skin lesion at the site of the proposed puncture or bordering on the puncture site; severe arterial hypotension (cardiogenic or hypovolemic shock); bleeding disorder or concomitant anticoagulant therapy.
Carefully. Severe cardiovascular failure (progression is possible), heart block, renal failure, general severe condition, decreased hepatic blood flow (for example, with heart failure, liver disease), concurrent administration of antiarrhythmic drugs (including beta-blockers), and other local anesthetics or drugs structurally similar to local amide type anesthetics (the possibility of developing an additive toxic effect), the need for paracervical anesthesia, pregnancy III trimester, inflammatory diseases Ania or infection of the injection site (for infiltration anesthesia), advanced age (over 65 years), children aged 5 to 12 years; with epidural administration (caudal and lumbar anesthesia) - previous neurological diseases, arterial hypotension, difficulty in puncture due to spinal deformity; with subarachnoid administration - AV block, subarachnoid hemorrhage, arterial hypotension, septicemia, multiple sclerosis, hemiplegia, paraplegia, neuromuscular disorders.
Dosage
The concentration of the solution used depends on the type of anesthesia: infiltration - 0.25-0.5%, conductive - 0.25-0.5%, retrobulbar - 0.75%, vagosympathetic blockade - 0.25%, epidural lumbar anesthesia - 0.1-0.75%, caudal - 0.25-0.5%. When carrying out epidural lumbar anesthesia: to obtain only the sensitive block, use 20-40 ml of a 0.25% solution with repeated administration every 3 hours; to obtain a partial motor block, 10-20 ml of a 0.5% solution is administered with repeated administration every 3 hours; to obtain a complete motor block - 10-20 ml of a 0.75% solution. In children weighing more than 10 kg, a single dose for epidural anesthesia is 1-2.5 mg / kg in the form of a 0.125-0.25% solution. To maintain epidural anesthesia, the administration of 0.2-0.4 mg https://zentherapycenter.com/let-j/jafzen.php kg / h in the form of 0.15%, 0.125-0.25% solution is used. The maximum dose is 0.4 mg / kg / h.
For lumbar anesthesia in obstetrics, a continuous infusion of 1-3 ml / h of 0.625% or 5-15 ml / h of 0.125% solutions is used. When conducting caudal anesthesia, 15-30 ml of a 0.25% solution of bupivacaine is used to obtain a partial motor block with repeated administration every 3 hours, 15-30 ml of a 0.5% solution to obtain a complete motor block with repeated administration every 3 hours.
For caudal anesthesia in children weighing more than 10 kg, a single dose is 1-2.5 mg / kg in the form of 0.125-0.25% solution. To maintain caudal anesthesia, the introduction of 0.2-0.4 mg / kg / h in the form of 0.1%, 0.125-0.25% solution is used. With repeated administration, the maximum dose is 0.4 mg / kg / h.
For caudal anesthesia in children weighing up to 10 kg, 1-1.25 mg / kg is administered in the form of a 0.125-0.25% solution. To maintain caudal anesthesia - 0.1-0.2 mg / kg / h in the form of 0.1%, 0.125-0.25% Bupivacaine. The maximum dose is 0.2 mg / kg / h.
For local infiltration anesthesia, a single injection of up to 70 ml of a 0.25% solution is used. In children - 0.5-2.5 mg / kg 0.25-0.5% solution.
To obtain a complete motor block during conduction anesthesia in adult patients, 5-70 ml of a 0.25% make use or 5-35 ml of a 0.5% solution are used. The introduction of these doses can be repeated every 3 hours. In children, conductive anesthesia is used in doses of 0.3-2.5 mg / kg in the form of a 0.25-0.5% solution.
For retrobulbar (regional) block, 2-4 ml of 0.75% solution is used.
To initiate a vagosympathetic block, 20 to 50 ml of a 0.25% solution is used with repeated administration every 3 hours.
For spinal anesthesia, a 0.5% isobaric solution (based on a 0.9% NaCl solution) and a 0.5% hyperbaric solution (based on an 8% dextrose solution) are used.
The maximum doses for adults are: single - 150 mg, daily - 400 mg.
Maximum doses for children when using bupivacaine for local or conduction anesthesia: single - 1 ml / kg as a 0.25% solution, when using a 0.5% solution of bupivacaine - 0.5 ml / kg.
Side effects
From Bupivacaine central and peripheral nervous system: post-puncture headache, dizziness, drowsiness, convulsions (the risk of their development increases with hypercapnia and acidosis), tremors, diplopia, tinnitus and tinnitus, paraplegia, paresis, dysesthesia, neuropathy, arachnoiditis, syndrome ponytail (lower limb paralysis, paresthesia), respiratory depression, unintentional total spinal block, numbness of the tongue, involuntary urination, involuntary defecation, urinary retention. From the CCC: lowering blood pressure, ventricular arrhythmia, bradycardia, blockade, cardiac arrest.
From the digestive system: nausea, vomiting. Allergic reactions: itching of the skin, skin rash, other anaphylactic reactions (most often anaphylactic shock), urticaria (on the skin and mucous membranes).
Other: muscle weakness, pain in the lumbar region.
Overdose. Symptoms: apnea, cardiotoxic effect, heart failure, methemoglobinemia, convulsions.
Treatment: maintaining adequate ventilation and cramping. Ventilation should be accompanied by oxygenation. With the development of seizures - in / in the introduction of suxamethonium - 50-100 mg and / or 5-15 mg of diazepam, 100-200 mg of thiopental can be used. With the development of ventricular fibrillation or cardiac arrest, resuscitation is necessary. Possible administration in repeated doses of sodium bicarbonate.
Interaction
Use with MAO inhibitors (furazolidone, procarbazine, selegiline) increases the risk of an excessive decrease in blood pressure. Vasoconstrictors (epinephrine, methoxamine, phenylephrine) prolong the local anesthetic effect of low-concentration (0.125-0.25%) bupivacaine solutions.
Local anesthetics increase CNS depression caused by drugs, CNS depressants.
Anticoagulants (ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin) increase the risk of bleeding. When treating the injection site of local anesthetic with disinfectant solutions containing heavy metals, the risk of developing a local reaction in the form of pain and swelling increases.
When 0.5% local anesthetics for spinal and epidural anesthesia with guanadrell, guanethidine, mecamylamine, trimethafan, the risk of a pronounced decrease in blood pressure and bradycardia is increased. Combination with halotane general inhalation anesthesia increases the risk of developing cardiotoxicity of bupivacaine. Strengthens and lengthens the effect of muscle relaxant drugs. With narcotic analgesics - an additive effect develops, which is used during epidural anesthesia, but respiratory depression is enhanced.
It exhibits antagonism with anti-myasthenic drugs 0.5% its effect on skeletal muscles, especially when used in high doses, which requires additional correction of the treatment of myasthenia gravis. Cholinesterase inhibitors (anti-myasthenic drugs, cyclophosphamide, demekarin, ecothiophate, isoflurophate, thiotepa) reduce the metabolism of local anesthetics.
special instructions
When carrying out epidural anesthesia, it is necessary to conduct a test dose with 3-5 ml. During the test dose for 5 min, it is necessary to maintain verbal contact with the patient and regularly determine heart rate. Aspiration should be carried out before the introduction of the main dose, which should be administered slowly, under constant monitoring.
When minimal toxic effects appear, further administration is Bupivacaine.
In the practice of spinal anesthesia, bupivacaine is a drug with minimal local toxicity.
The drug is more cardiotoxic than other locally anesthetizing drugs (possible AV block, ventricular arrhythmias, including ventricular fibrillation and alternative arrest), therefore, when using it, aspiration tests should be performed repeatedly.
Paracervical blockade can affect the fetus to a greater extent than other blockades. 0.75% solution is not used in obstetric practice due to frequent cases of the development of cardiac arrest and breathing in patients. The introduction of small doses for local anesthesia in the head, neck, as well as in the retrobulbar space or the region of the stellate ganglion can give a negative reaction similar to the systemic toxic effect (up to respiratory arrest), and therefore it related pill necessary to have the necessary drugs and equipment ready.
The effectiveness of adding a vasoconstrictor has been proven only for low concentrated solutions (0.125-0.25%). Upon reaching analgesia, such solutions retain motor function and can be recommended for regional anesthesia in the postoperative period and in obstetric practice.
Patients require control of the CCC, respiratory system and central nervous system.
MAO inhibitors must be withdrawn 0.5% days before the administration of a local anesthetic.
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.
