Bupivacaine Recordati

Package leaflet: Information for the patient

Bupivacaine Recordati 5 mg/ml injectable solution, hyperbaric

bupivacaine hydrochloride
Generic medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Bupivacaine Recordati is and what it is used for
2. What you need to know before using Bupivacaine Recordati
3. How to use Bupivacaine Recordati
4. Possible side effects
5. How to store Bupivacaine Recordati
6. Contents of the pack and other information

1. What Bupivacaina Recordati is and what it is used for

Bupivacaina Recordati contains the active substance bupivacaine hydrochloride, which belongs to a class of medicines called local anaesthetics that cause loss of sensation in the area of the body being treated.
Bupivacaina Recordati is indicated for all surgical procedures involving:

• General surgery
• Bones (orthopaedics)
• Eye (ophthalmology)
• Nose, mouth and throat (otorhinolaryngology)
• Teeth and mouth (stomatology)
• Pregnancy, childbirth and female genital system (obstetrics and gynaecology)
• Skin (dermatology).

Bupivacaina Recordati may be used either alone or in combination with medicines that cause loss of sensation throughout the body (general anaesthetics).
Bupivacaina Recordati hyperbaric injectable solution is indicated for a particular type of anaesthesia, selective spinal block.

2. What you should know before using Bupivacaine Recordati

Do not use Bupivacaine Recordati

• if you are allergic to bupivacaine or to any of the other ingredients of this medicinal product (listed in section 6)
• if you are allergic to other local anesthetics of the same type as Bupivacaine Recordati or to similar substances
• in certain conditions such as paracervical block and regional intravenous anesthesia (Bier Block), as accidental leakage of bupivacaine into the circulation could cause acute systemic toxic reactions.

If your doctor administers Bupivacaine Recordati hyperbaric injectable solution to you,
the medicine is also contraindicated in the following cases:

• acute diseases of the nervous system (such as meningitis, tumors, poliomyelitis, and intracranial hemorrhage)
• spinal column disorders (spinal stenosis and active spinal diseases, for example spondylitis, tuberculosis, tumor) or recent trauma (e.g., fractures)
• widespread infection (septicemia)
• blood red cell disorder (pernicious anemia combined with subacute degeneration of the spinal cord)
• skin infection at the injection site or surrounding area
• severe depression of heart function or severe reduction in circulating blood volume (cardiogenic or hypovolemic shock)
• blood coagulation disorders or ongoing treatment with blood-thinning medicines (anticoagulants).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Bupivacaine Recordati.
Some local anesthesia techniques may be associated with adverse reactions such as cardiac arrest
or death following the use of bupivacaine.
Following high blood concentrations of bupivacaine, disturbances in heart rhythm (ventricular arrhythmia, ventricular fibrillation), severe and sudden reduction in blood circulation (cardiovascular collapse), and death have been reported.
However, at the doses of Bupivacaine Recordati hyperbaric injectable solution normally used, high blood concentrations are not expected.
Anesthesia procedures must always be performed in adequately equipped settings and by qualified personnel. The medicine will be administered to you by a doctor trained in the procedure and experienced in diagnosing and managing adverse effects.
Although local anesthesia often represents the best technique, your doctor will carefully evaluate your health status, with special attention, to reduce the risk of dangerous side effects if:

• you are elderly or debilitated
• you have partial or complete heart block
• you have advanced liver disease
• you have severe kidney function impairment
• you are in an advanced stage of pregnancy
• you have reduced blood volume (hypovolemia) and need to be treated with Bupivacaine Recordati hyperbaric injectable solution
• you are being treated with medicines that regulate heart rhythm (class III antiarrhythmics, for example amiodarone); in such cases, your doctor will perform frequent checks and may consider performing an electrocardiogram
• you are scheduled to undergo a type of anesthesia called stellate ganglion block.

Some local anesthesia techniques may be associated with severe adverse reactions,
regardless of the medicine used, for example:

• reduced cardiovascular function, especially in the presence of reduced blood volume (hypovolemia)
• very rare cases (during injections into the eye globe): temporary blindness, cardiovascular collapse, absence of breathing (apnea), seizures, etc.
• prolonged muscular dysfunction in the eyes (during injections into the eye globe)
• decreased (bradycardia) and increased (tachycardia) fetal heart rate
• stellate ganglion block may cause side effects similar to those of central nerve block, as well as cardiac toxicity with increased or decreased heart rate up to cardiac arrest

A rare but serious adverse reaction following administration of Bupivacaine hyperbaric
injectable solution is reduced cardiovascular and respiratory activity. The onset of altered
sensation (paresthesia), anesthesia, motor weakness, and paralysis are rare complications. Occasionally, such damage may be permanent.
Hypotension (reduced blood pressure) and bradycardia (reduced heart rate) have also been observed.
If you suffer from neurological diseases (such as multiple sclerosis, hemiplegia, paraplegia, and neuromuscular disorders), this medicine should be administered with particular caution, especially in case of intrathecal injection.

Other medicines and Bupivacaine Recordati
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Bupivacaine Recordati should be used with caution if:

• you are being treated with other local anesthetics
• you are taking medicines that regulate heart rhythm (such as lidocaine, mexiletine, and tocainide, class III antiarrhythmics such as amiodarone)
• you are being treated with medicines for depression (MAO inhibitors or tricyclic antidepressants).

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding,
ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
In patients in an advanced stage of pregnancy, the dose for spinal anesthesia should be reduced
(see also “Warnings and precautions”).
Adverse effects on the fetus due to local anesthetics, such as reduced fetal heart rate (fetal bradycardia), may result from high concentrations of anesthetic reaching the fetus.
Breastfeeding
Like other local anesthetics, bupivacaine may be excreted in breast milk, but in such small amounts that there is generally no risk to the newborn.

Driving and using machines
Bupivacaine Recordati may impair your ability to drive vehicles or operate machinery.
Bupivacaine Recordati may have a very slight effect on mental function and coordination and may temporarily negatively affect movement and level of alertness.

Bupivacaine Recordati 5 mg/ml solution for injection contains 8 mg of sodium per ml. This should be taken into consideration in patients with impaired renal function or those on a low-sodium diet.

3. How to use Bupivacaine Recordati

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The dose is determined by the doctor and generally ranges from 2–3 mg to 100–150 mg depending on the
type of anesthesia required.
The maximum recommended dose for an adult and for a single administration should not exceed 150 mg,
corresponding to 30 ml of the 5 mg/ml solution; more generally, the recommended safe dose not to be
exceeded, both for adults and children, is 2 mg/kg per single administration.
For more detailed information, see the section at the end of this leaflet.
Use in children
The dose is determined by the doctor.
If you use more Bupivacaine Recordati than you should
In case of overdose, symptoms may appear later than the administration (15–60 minutes after injection).
If you have any doubts about the use of Bupivacaine Recordati, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
With Bupivacaine Recordati, toxic and allergic reactions may occur.
Reported toxic reactions include:
excitation, tremors, disorientation, dizziness, pupil dilation (mydriasis), increased metabolism and body temperature, and, at very high doses, muscle rigidity of the jaw (trismus) and convulsions, sweating, changes in heart rhythm (arrhythmias), increased blood pressure (hypertension), increased respiratory rate (tachypnea), bronchial dilation (bronchodilation), nausea and vomiting, slowing of the heart rate (bradycardia), and vasodilation.
Allergic reactions mostly occur in hypersensitive individuals, but many cases have also been reported in subjects without a history of hypersensitivity. Allergic manifestations include:
various types of skin rash (urticaria, pruritus), bronchospasm, throat swelling (laryngeal edema), collapse of heart and lung function (cardiorespiratory collapse due to anaphylactic shock).

Other side effects of the medicine:
Very common (may affect more than 1 in 10 people)

• reduction in blood pressure (hypotension)
• nausea.

Common (may affect up to 1 in 10 people)

• altered sensation in limbs and other body parts (paraesthesiae)
• dizziness
• reduced heart rate (bradycardia)
• increased blood pressure (hypertension)
• vomiting.

Uncommon (may affect up to 1 in 100 people)

• convulsions
• altered sensation around the mouth (circumoral paraesthesia)
• tongue numbness
• increased sensitivity to sounds (hyperacusis)
• visual disturbances
• loss of consciousness
• tremor
• sensation of emptiness in the head
• ringing in the ears (tinnitus)
• speech disorders (dysarthria).

Rare (may affect up to 1 in 1,000 people)

• allergic reactions
• severe and sudden allergic reaction (anaphylactic shock)
• nerve damage (neuropathy)
• injury to peripheral nerves
• inflammation of one of the membranes surrounding the brain (arachnoiditis)
• reduced motor function (paresis)
• paralysis of the lower part of the body (paraplegia)
• respiratory arrest and cessation of heart and blood circulation function (unintentional total spinal block)
• double vision
• cardiac arrest
• changes in heart rhythm
• respiratory depression.

In addition to the side effects listed above, the following have been observed with Bupivacaine Recordati hyperbaric injectable solution:
Common (may affect up to 1 in 10 people)

• headache (post-dural puncture headache)
• urinary retention, urinary incontinence.

Uncommon (may affect up to 1 in 100 people)

• reduced motor function (paresis)
• heightened sensation in an area of the body (dysaesthesia)
• muscle weakness
• back pain.

Rare (may affect up to 1 in 1,000 people)

• paralysis.

For information regarding effects due to acute systemic toxicity, see the end of this leaflet.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bupivacaine Recordati

Store below 30°C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after “Exp.”.
The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Bupivacaine Recordati contains
Bupivacaine Recordati 5 mg/ml injectable solution:

• The active substance is bupivacaine hydrochloride. 1 ml of solution contains 5 mg of bupivacaine hydrochloride.
• The other components are: sodium chloride, water for injections.

Bupivacaine Recordati 5 mg/ml hyperbaric injectable solution:

• The active substance is bupivacaine hydrochloride. 1 ml of solution contains 5 mg of bupivacaine hydrochloride.
• The other components are: monohydrate glucose, water for injections.

Description of the appearance of Bupivacaine Recordati and contents of the pack
Bupivacaine Recordati 5 mg/ml injectable solution: 10 vials of 10 ml
Bupivacaine Recordati 5 mg/ml hyperbaric injectable solution: 10 vials of 4 ml
Marketing Authorization Holder
Recordati Industria Chimica Farmaceutica S.p.A. - via Matteo Civitali, 1 - 20148 Milan.
Manufacturer
Savio Industrial s.r.l. – via E. Bazzano, 14 – 16019 Ronco Scrivia (GE).

The following information is intended exclusively for physicians or healthcare professionals:
Therapeutic indications
Bupivacaine Recordati may be used for all types of peripheral anaesthesia:

• Local infiltration, loco-regional, nerve block
• Sympathetic block
• Epidural, sacral
• Spinal subarachnoid

Hyperbaric Bupivacaine Recordati is indicated when a selective spinal block is desired.
Contraindications
Hypersensitivity to the active substance, to other amide-type local anaesthetics, to other substances closely
related from a chemical standpoint, or to any of the excipients listed in section 6.
The product is also contraindicated in paracervical block and in regional intravenous anaesthesia (Bier
block), since accidental loss of bupivacaine into the circulation could cause acute systemic toxic reactions.
General contraindications must be considered in case of intrathecal anaesthesia:

• active acute diseases of the central nervous system, such as meningitis, tumours, poliomyelitis and intracranial haemorrhage;
• spinal stenosis and active spinal disease (e.g. spondylitis, tuberculosis, tumour) or recent trauma (e.g. fractures);
• septicaemia;
• pernicious anaemia combined with subacute degeneration of the spinal cord;
• pyogenic skin infection at the injection site or surrounding area;
• cardiogenic or hypovolemic shock;
• coagulation disorders or ongoing anticoagulant therapy.

Warnings and precautions
Cases of cardiac arrest or death following the use of bupivacaine for epidural anaesthesia or peripheral nerve block have been reported. In some cases, resuscitation proved difficult or impossible despite apparently adequate preparation and management by medical staff (see “Contraindications”).
Intrathecal anaesthesia must be performed only by a physician or under the supervision of clinicians with the necessary competence and experience.
Bupivacaine, like all local anaesthetics, when used in anaesthetic procedures leading to high blood concentrations of the drug, may cause acute toxic effects on the central nervous system and cardiovascular system, particularly in case of accidental intravascular injection or injection into highly vascularized areas. Ventricular arrhythmias, ventricular fibrillation, sudden cardiovascular collapse and death have been reported following high systemic concentrations of bupivacaine. However, at the doses normally used for intrathecal anaesthesia, high systemic concentrations are not expected.
Regional anaesthesia procedures must always be performed in adequately equipped settings and by qualified personnel. Immediate availability of equipment and medications necessary for monitoring and emergency resuscitation is required.
In patients undergoing major nerve block or receiving high doses of the drug, an intravenous catheter should be inserted before administration of the local anaesthetic. The physician must have received complete and adequate training in the procedure to be used and must be experienced in the diagnosis and treatment of adverse effects, systemic toxicity, or other complications.
Peripheral major nerve blocks may involve administration of a large volume of local anaesthetic into highly vascularized areas, often near large vessels, where there is an increased risk of intravascular injection and/or rapid systemic absorption, potentially leading to high plasma concentrations.
Although regional anaesthesia frequently represents the anaesthetic technique of choice, some patients require special attention to reduce the risk of dangerous side effects:

• elderly or debilitated patients;
• patients with partial or complete heart block, as local anaesthetics may depress cardiac conduction;
• patients with advanced liver disease or severe renal function impairment;
• patients in advanced stages of pregnancy;
• hypovolemic patients may develop severe and sudden hypotension during intrathecal anaesthesia, regardless of the local anaesthetic used. Hypotension is commonly observed after intrathecal block in adults;
• patients receiving class III antiarrhythmic drugs (e.g. amiodarone) should be closely monitored and ECG monitoring should be considered, as cardiac effects may be additive.

Some local anaesthesia techniques may be associated with severe adverse reactions, regardless of the local anaesthetic used:

• Central nerve block: may cause cardiovascular depression, especially in the presence of hypovolemia. Epidural anaesthesia should therefore be used with caution in patients with impaired cardiovascular function.
• Retrobulbar injections: very rarely, may reach the cerebral subarachnoid space, causing temporary blindness, cardiovascular collapse, apnea, seizures, etc. Such reactions must be diagnosed and treated immediately.
• Retro- and peribulbar injections of local anaesthetics: carry a low risk of persistent ocular muscle dysfunction. Primary causes include trauma and/or local toxic effects on muscles and/or nerves. The severity of such tissue reactions correlates with the extent of trauma, the concentration of local anaesthetic, and the duration of tissue exposure to the local anaesthetic. As with all local anaesthetics, it is therefore necessary to use the lowest doses and

concentrations capable of achieving the desired effect. Vasoconstrictors
may exacerbate tissue reactions and should only be used if indicated.
Local anaesthetics, even at low doses, when injected into the head and neck, such as during stellate ganglion blocks, may produce systemic toxicity due to inadvertent intra-arterial injection or intravascular reabsorption or entry into the subarachnoid space.

• Paracervical block may occasionally cause fetal bradycardia/tachycardia. Careful monitoring of fetal heart rate is therefore necessary.
• Continuous intra-articular infusion is not an approved indication for Bupivacaine Recordati. However, post-marketing cases of chondrolysis have been reported exclusively in North America in patients who received continuous post-operative intra-articular infusion of local anaesthetics. The majority of reported chondrolysis cases involved the shoulder joint. A causal relationship has not been established.

A rare but serious adverse reaction following spinal anaesthesia is total or high spinal block and
consequent cardiovascular and respiratory depression. Cardiovascular depression is caused by
extensive sympathetic block leading to profound hypotension and bradycardia or even cardiac
arrest. Respiratory depression may be caused by blockade of innervation to respiratory muscles,
including the diaphragm. The risk of total or high spinal block is higher in elderly patients or those
in advanced stages of pregnancy. In these patients, the dose should therefore be reduced.
The onset of neurological damage is a rare consequence of intrathecal anaesthesia and may result in
paresthesia, anaesthesia, motor weakness, and paralysis. Occasionally, such damage may be permanent.
Caution is recommended in patients with neurological disorders such as multiple sclerosis, hemiplegia,
paraplegia, and neuromuscular disorders, even though intrathecal anaesthesia is not believed to
negatively affect such conditions. Before initiating treatment, it should be considered whether
the benefits outweigh the potential risks for the patient.
Epidural anaesthesia may cause hypotension and bradycardia. The risk can be reduced by preloading the circulation with crystalloid or colloid solutions. Hypotension should be treated immediately with intravenous administration, possibly repeated, of a sympathomimetic agent. In children, dosage must be adjusted according to age and weight.
When bupivacaine is administered intra-articularly, caution is advised if recent major intra-articular trauma is suspected or when surgical intervention has resulted in extensive joint exposure, as this may accelerate absorption and lead to higher plasma concentrations.
When performing infiltrations for local anaesthesia in areas lacking collateral circulation (fingers, penile base, etc.), it is a precautionary measure to use the anaesthetic without vasoconstrictor to avoid ischemic necrosis.
Bupivacaine Recordati must be used with extreme caution in patients receiving treatment with MAO inhibitors or tricyclic antidepressants.
Before use, the physician must verify the circulatory status of the patient. Any overdose of anaesthetic must be avoided, and two maximum doses should never be administered without an interval of at least 24 hours.
It is, however, necessary to use the lowest doses and concentrations that allow the desired effect to be achieved.
An adequate test dose, preferably combined with adrenaline, is advisable to promptly detect accidental intravenous or intrathecal injection.
The anaesthetic solution should be injected cautiously in small increments, after approximately 10 seconds of prior aspiration. Especially when infiltrating highly vascularized areas, it is advisable to wait approximately 2 minutes before proceeding with the actual loco-regional block.
The patient must be kept under close surveillance, with immediate discontinuation of administration at the first sign of alarm (e.g. altered consciousness).
Immediate availability of equipment, medications, and qualified personnel for emergency treatment is required, as serious, sometimes fatal, reactions have been reported following the use of local anaesthetics, even in the absence of individual hypersensitivity in the patient's history.
Posology and method of administration
Bupivacaine Recordati is usually used in minimal dosages, varying according to indication, from 2–3 mg to 100–150 mg, as indicated in the following table for guidance purposes.

The solubility of bupivacaine at pH greater than 6.5 is limited. This should be taken into consideration when alkaline solutions, such as carbonates, are added, as they may cause precipitation of the solution.
The solutions contain no preservatives, are for single use only, and must be used immediately after opening. Any residual medicinal product must be discarded.
Bupivacaina Recordati vials must not be resterilized.
The maximum dosage for an adult and per single administration should not exceed 150 mg, corresponding to 30 ml of solution; more generally, the recommended safe dose, both for adults and children, not to be exceeded, is 2 mg/kg per single administration.
In prolonged analgesic therapy, doses usually range from 0.25 to 1 mg/kg body weight; administration may be repeated 2–3 times within 24 hours.
N.B. When performing prolonged blocks by repeated bolus injections, the risk of achieving toxic plasma concentrations or inducing local neurotoxicity must be considered.
The dose to be administered must be calculated based on the physician’s experience and knowledge of the patient’s clinical condition. The lowest effective dose that provides adequate anesthesia should be used. Individual variations in onset time and duration may occur. In children with high body weight, a gradual dose reduction is often necessary, based on ideal body weight. Reference texts should be consulted regarding both factors influencing specific block techniques and individual patient requirements. The extent of anesthesia spread is difficult to predict but is influenced by the volume of drug administered, especially with isobaric solutions.
To prevent accidental intravascular injection, aspiration should be performed before and during administration of the main dose, which must be injected slowly or in incremental doses. During the procedure, monitor the patient’s vital signs carefully and maintain verbal contact.
When epidural anesthesia is required, it is recommended to precede it with a test dose of 3–5 ml of bupivacaine with adrenaline. Accidental intravascular injection may be recognized by a transient increase in heart rate; accidental intrathecal injection is identified by signs of spinal block. At the first sign of toxicity, administration must be immediately discontinued (see section “Undesirable effects”).

Overdose
Accidental intravascular injection of local anesthetics may cause immediate systemic toxic reactions (occurring within seconds to a few minutes).
In cases of overdose, systemic toxicity manifests later (15–60 minutes after injection), due to a slow rise in blood levels of the local anesthetic.
Bupivacaina Recordati hyperbaric, under recommended conditions of use, is unlikely to promote blood levels high enough to cause systemic toxicity. However, if other local anesthetics are administered concomitantly, toxic effects are additive and may lead to systemic toxicity.
In the event of suspected overdose, administration must be stopped at the first warning sign, the patient placed in a horizontal position, and airway patency ensured, with oxygen administered in case of severe dyspnea or artificial ventilation (Ambu bag).
The use of bulbar analeptics should be avoided, as they may worsen the condition by increasing oxygen consumption.
Seizures, if they occur, may be controlled with intravenous diazepam at a dose of 10–20 mg; barbiturates are not recommended, as they may exacerbate bulbar depression. Circulation may be supported by appropriate intravenous doses of corticosteroids; diluted solutions of alpha-beta-agonists with vasoconstrictor action (mephentermine, metaraminol, and others) or atropine sulfate may be added. Sodium bicarbonate, administered intravenously at targeted concentration, may be used as an antiacidotic agent.

Possible undesirable effects
The adverse reaction profile of Bupivacaina Recordati is similar to that of other long-acting local anesthetics. Adverse drug reactions are difficult to distinguish from the physiological effects resulting from nerve conduction block (such as decreased arterial pressure, bradycardia, temporary urinary retention), from events directly caused by injection (e.g., nerve fiber trauma, spinal hematoma), indirectly (e.g., epidural abscess and meningitis), or from events associated with cerebrospinal fluid loss (e.g., post-dural puncture headache).
The occurrence of neurological damage is a rare but well-known consequence of regional anesthesia, particularly epidural and spinal anesthesia.

Acute systemic toxicity
Systemic toxic reactions primarily affect the central nervous system and the cardiovascular system. These reactions are caused by high blood concentrations of the local anesthetic following accidental intravascular injection, overdose, or unusually rapid absorption from highly vascularized areas. Central nervous system reactions are similar to those of other amide-type local anesthetics, while cardiac reactions depend more significantly—both quantitatively and qualitatively—on the specific drug.
Bupivacaina Recordati hyperbaric, under recommended conditions of use, is unlikely to promote blood levels high enough to cause systemic toxicity. However, if other local anesthetics are administered concomitantly, toxic effects are additive and may lead to systemic toxicity.
Toxicity affecting the central nervous system manifests gradually, with symptoms and signs of increasing severity. Initial symptoms typically include circumoral paresthesia, tongue numbness, a sensation of emptiness in the head, hyperacusis, tinnitus, and visual disturbances. Dysarthria, muscle twitching, or tremor represent more severe manifestations and precede generalized seizures. These signs should not be mistaken for hysterical behavior. Unconsciousness and convulsive seizures may follow, lasting from a few seconds to several minutes. After seizures, due to increased muscular activity, respiratory interference, and possible airway obstruction, hypoxia and hypercapnia develop rapidly. In severe cases, apnea may occur. Acidosis, hyperkalemia, hypocalcemia, and hypoxia increase and amplify the toxic effects of local anesthetics.
Return to baseline clinical condition follows redistribution of the local anesthetic from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid if large amounts of the drug have not been administered.
In severe cases, cardiovascular effects may occur, usually preceded by signs of central nervous system toxicity. In deeply sedated patients or those under general anesthesia, cardiovascular effects may appear without preceding central nervous system prodromal signs. As a result of high systemic concentrations of local anesthetics, hypotension, bradycardia, arrhythmias, and even cardiac arrest may occur; in rare cases, cardiac arrest has occurred without preceding central nervous system symptoms.
In children, early signs of systemic local anesthetic toxicity may be difficult to detect when the block is administered during general anesthesia.

Treatment of acute systemic toxicity
Administration of the local anesthetic must be immediately discontinued if signs of acute systemic toxicity or total spinal block appear. Symptoms of central nervous system toxicity (seizures, central nervous system depression) must be treated immediately with adequate airway and respiratory support and administration of anticonvulsants such as intravenous diazepam at a dose of 10–20 mg; barbiturates are not recommended, as they may worsen bulbar depression. Circulation may be supported with appropriate intravenous doses of corticosteroids; diluted solutions of alpha-beta-agonists with vasoconstrictor action (mephentermine, metaraminol, and others) or atropine sulfate may be added.
If circulatory arrest occurs, immediate cardiopulmonary resuscitation must be initiated. Ensuring optimal oxygenation, supporting ventilation and circulation, and treating acidosis are vital.
If cardiovascular depression (hypotension, bradycardia) occurs, appropriate treatment with intravenous fluids, vasopressors, and/or inotropic agents should be considered.
In children, dosing must be adjusted according to age and weight.
If cardiac arrest occurs, resuscitation efforts may need to be prolonged to achieve a favorable outcome.
Note: italicized text refers only to the hyperbaric formulation