BUPIVACAINA 5 mg /Ml Roztwór Do Wstrzykiwań

Treść ulotki

1. Bupivacaina Recordati 5 mg/ml injectable solution, hyperbaric
   1. What is Bupivacaina Recordati and what is it used for
   2. What you need to know before using Bupivacaina Recordati
   3. How to use Bupivacaina Recordati
   4. Possible side effects
   5. How to store Bupivacaina Recordati
   6. Contents of the pack and other information

Bupivacaina Recordati 5 mg/ml injectable solution, hyperbaric

bupivacaine hydrochloride

Equivalent Medicinal Product

Read this leaflet carefully before using this medicine as 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 pass it on to others, even if they have the same symptoms as you, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

Bupivacaina Recordati contains the active ingredient bupivacaine hydrochloride, which belongs to a class
of medicines called local anesthetics that cause loss of sensation in the area of the body
affected by the treatment.
Bupivacaina Recordati is indicated in all surgical procedures concerning:

• General surgery
• Bones (orthopedics)
• Eye (ophthalmology)
• Nose, mouth and throat (otorhinolaryngology)
• Teeth and mouth (dentistry)
• Pregnancy, childbirth and female genital apparatus (obstetrics and gynecology)
• Skin (dermatology).

Bupivacaina Recordati can be used alone or in combination with medicines that eliminate
sensitivity throughout the body (general anesthetics).
Bupivacaina Recordati hyperbaric injectable solution is indicated in a particular type of anesthesia, spinal
blockade.

2. What you need to know before using Bupivacaina Recordati

Do not use Bupivacaina Recordati

• if you are allergic to bupivacaine or any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to other local anaesthetics of the same type as Bupivacaina Recordati or to other similar substances
• in certain conditions such as paracervical block and regional intravenous anaesthesia (Bier Block) as accidental loss of bupivacaine into the circulation could cause acute systemic toxic reactions.

If your doctor will perform the treatment with Bupivacaina Recordati hyperbaric injectable solution, the medicine is also contraindicated in the following cases:

• acute ongoing diseases of the nervous system (such as meningitis, tumours, poliomyelitis and intracranial haemorrhages)
• diseases of the spinal cord (spinal stenosis and active diseases of the spinal cord, for example spondylitis, tuberculosis, tumour) or recent trauma (for example fractures)
• widespread infection (septicemia)
• blood red cell disease (pernicious anaemia combined with subacute spinal cord degeneration)
• skin infection at the injection site or in the surrounding area
• severe depression of heart activity or severe reduction of blood volume in circulation (cardiogenic or hypovolaemic shock)
• disorders of blood coagulation or ongoing treatments with medicines that thin the blood (anticoagulants).

Warnings and precautions
Consult your doctor or pharmacist or nurse before using Bupivacaina Recordati.
Some local anaesthesia techniques may be associated with adverse reactions such as cardiac arrest
or death following the use of bupivacaine.
Following high concentrations of bupivacaine in the blood, altered heart rhythm (ventricular arrhythmia, ventricular fibrillation), severe and sudden reduction of blood distribution in the body (cardiovascular collapse) and death have been reported.
However, at the doses of Bupivacaina Recordati hyperbaric injectable solution normally used, high concentrations in the blood are not expected.
Anaesthesia procedures must always be performed in adequately equipped areas and by
qualified personnel. The medicine will be administered to you by a doctor trained in the procedure to be used and experienced in the diagnosis and treatment of undesirable effects.
Although local anaesthesia frequently represents the best technique, the doctor will check your
state of health with special attention, in order to reduce the risk of dangerous side effects if:

• you are elderly or debilitated
• you have partial or complete heart function block
• you have advanced liver diseases
• you have severe kidney function disorders
• you are in advanced state of pregnancy
• you have reduced blood volume (hypovolaemia) and must be treated with Bupivacaina Recordati hyperbaric injectable solution
• you are being treated with medicines that regulate the heart rhythm (class III antiarrhythmics, for example amiodarone), in these cases the doctor will perform numerous checks and consider the possibility of performing an electrocardiogram.
• you will have to undergo an anaesthesia called stellate ganglion block.

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

• reduction of cardiovascular function, especially in the presence of a reduction in blood volume (hypovolaemia)
• in very rare cases (during injections into the eyeball), temporary blindness, cardiovascular collapse, absence of breathing (apnea), convulsions, etc.
• prolonged muscle dysfunction at the level of the eyes (during injections into the eyeball)
• decrease (bradycardia) and increase (tachycardia) in the fetal heart rate
• stellate ganglion block may give undesirable effects similar to those of central nervous system block as well as cardiac toxicity with increased or decreased heart rate up to cardiac arrest

A rare but serious adverse reaction following the administration of Bupivacaina hyperbaric injectable solution is the reduction of cardiovascular and respiratory activity. Altered sensitivity (paraesthesia), anaesthesia, weakening of movements (motor weakness) and paralysis are rare damages. Occasionally these damages are permanent.
Reduction of blood pressure (hypotension) and reduction of heart rate (bradycardia) have also been observed.
If you suffer from neurological diseases (such as multiple sclerosis, hemiplegia, paraplegia and neuromuscular disorders) this medicine must be administered to you with particular caution, especially in the case of intratecal injection.

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

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

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
In patients in advanced state of pregnancy, the dose in case of (spinal) anaesthesia must be reduced
(see also “Warnings and precautions”).
Adverse effects on the fetus due to local anaesthetics, such as reduced fetal heart rate (fetal bradycardia), may be due to high concentrations of
anaesthetic reaching the fetus.
Breastfeeding
Like other local anaesthetics, 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
Bupivacaina Recordati impairs the ability to drive vehicles or operate machinery.
Bupivacaina Recordati may have a very mild effect on mental function and coordination and
may temporarily negatively affect movements and alertness.

Bupivacaina Recordati 5 mg/ml injectable solution contains 8 mg of sodium per ml.To be taken into
consideration in people with impaired renal function or who are following a low-sodium diet.

3. How to use Bupivacaina Recordati

Use this medicine following the instructions of your doctor or pharmacist exactly as given. If you have
any doubts, consult your doctor or pharmacist.
The dose is established by the doctor and generally varies from 2-3 mg to 100-150 mg depending on the type of
anesthesia to be performed.
The maximum recommended dose for an adult and for single administration should not exceed
150 mg, corresponding to 30 ml of the 5 mg/ml solution; more generally the safety dose, for both
adults and children, which is advisable not to exceed, is 2 mg/kg for single
administration.
For more detailed information, see what is reported at the end of this leaflet.

Use in children
The dose is established by the doctor.

If you use more Bupivacaina Recordati than you should
In case of overdose, symptoms may manifest even later than
administration (15-60 minutes after the injection).
If you have any doubts about the use of Bupivacaina Recordati, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
With Bupivacaina Recordati, toxic reactions and allergic reactions may occur. Among the toxic
reactions reported are:
excitement, tremors, disorientation, dizziness, dilation of the pupil (mydriasis), increased
metabolism and body temperature and, for very high doses, contraction of the jaw muscles (trismus) and
convulsions, sweating, alteration of the heart rhythm (arrhythmias), increased
blood pressure (hypertension), increased breathing rate (tachypnea), dilation of the
bronchi (bronchodilation), nausea and vomiting, slowing of the heartbeat (bradycardia) and
vasodilation.
Allergic reactions occur mostly in sensitive individuals, but many cases are reported
even in individuals who do not have a history of hypersensitivity. Allergic manifestations
include:
skin rashes of various types (urticaria, itching), spasm of the bronchi, swelling of the throat (laryngeal
edema), collapse of the heart and lungs (cardiorespiratory collapse from anaphylactic shock).
Other side effects of the medicine:
Very common (may affect more than 1 in 10 people)

• reduction of blood pressure (hypotension)
• nausea.

Common (may affect up to 1 in 10 people)

• altered sensitivity of the limbs and in other parts of the body (paresthesia)
• dizziness
• slowing of the heartbeat (bradycardia)
• increased blood pressure (hypertension)
• vomiting.

Uncommon (may affect up to 1 in 100 people)

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

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

• allergic reactions
• severe and sudden allergic reaction (anaphylactic shock)
• nerve damage (neuropathy)
• peripheral nerve injury
• inflammation of one of the membranes of the brain (arachnoiditis)
• decreased motility (paresis)
• paralysis of the lower part of the body (paraplegia)
• respiratory arrest and cessation of heart and blood circulation function (total spinal block unintentional)
• double vision
• heart arrest
• alteration of the heart rhythm
• depression of breathing.

In addition to the side effects listed above, with Bupivacaina Recordati hyperbaric injectable
solution the following have been observed:
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)

• decreased motility (paresis)
• amplification of sensitivity in an area of the body (dysesthesia)
• muscle weakness
• back pain.

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

• paralysis.

For information regarding effects due to acute systemic toxicity, see the end of this leaflet.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist or nurse. You can also report side effects
directly through 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 Bupivacaina Recordati

Store at a temperature below 30°C.
Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after “Exp.”.
The expiry date refers to the last day of that month.
Do not dispose of any medicine in waste water 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 Bupivacaina Recordati contains
Bupivacaina Recordati 5 mg/ml injectable solution:

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

Bupivacaina Recordati 5 mg/ml hyperbaric injectable solution:

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

Description of the appearance of Bupivacaina Recordati and contents of the pack
Bupivacaina Recordati 5 mg/ml injectable solution: 10 vials of 10 ml
Bupivacaina Recordati 5 mg/ml hyperbaric injectable solution: 10 vials of 4 ml

Marketing Authorisation 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 doctors or healthcare professionals:

Therapeutic indications
Bupivacaina Recordati can be used in all types of peripheral anesthesia:

• Local infiltration, locoregional, truncular
• Sympathetic block
• Peridural, sacral
• Spinal subarachnoid

Hyperbaric Bupivacaina Recordati is indicated when a selective spinal block is desired.

Contraindications
Hypersensitivity to the active ingredient, to other local anesthetics of the amide type, to other substances closely related from a chemical point of view or to any of the excipients listed in section 6.
The product is also contraindicated in paracervical block and in regional intravenous anesthesia (Bier Block) as accidental loss of bupivacaine into the circulation could cause acute systemic toxic reactions.

General contraindications must be taken into consideration in case of intrathecal anesthesia:

• acute active diseases of the central nervous system, such as meningitis, tumors, poliomyelitis and intracranial hemorrhages;
• spinal stenosis and active disease of the spine (e.g. spondylitis, tuberculosis, tumor) or recent trauma (e.g. fractures);
• septicemia;
• pernicious anemia combined with subacute degeneration of the spinal cord;
• pyogenic skin infection at the injection site or in the surrounding area;
• cardiogenic or hypovolemic shock;
• coagulation disorders or ongoing anticoagulant treatment.

Warnings and precautions
Cases of cardiac arrest or death have been reported following the use of bupivacaine for epidural anesthesia or peripheral nerve block. In some cases, resuscitation has proved difficult or impossible despite the preparation and conduct of the personnel appearing adequate (see “Contraindications”).

Intrathecal anesthesia must be performed only by a doctor or under the supervision of clinicians with the

necessary competence and experience.
Bupivacaine, like all local anesthetics, when used for local anesthetic procedures that determine high blood concentrations of the drug, can cause acute toxic effects on the central nervous system and the cardiovascular system, especially in case of accidental intravascular administration or injection into highly vascularized areas. Following high systemic concentrations of bupivacaine, ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported. However, at the doses normally used for

intrathecal anesthesia, high systemic concentrations are not expected.
Regional anesthesia procedures must always be performed in adequately equipped areas and by qualified personnel. Immediate availability of equipment and medicines necessary for monitoring and emergency resuscitation must be ensured.
In patients undergoing major block or receiving high doses of the drug, an intravenous catheter must be inserted before administration of the local anesthetic. The doctor must have received complete and adequate training on the procedure to be used and must be experienced in the diagnosis and treatment of adverse effects, systemic toxicity or other complications.
Blocking of major peripheral nerves may involve the administration of a large volume of local anesthetic in highly vascularized areas, often near large vessels where there is an increased risk of intravascular injection and/or rapid systemic absorption, which can lead to elevated plasma concentrations.
Although regional anesthesia frequently represents the anesthetic 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 anesthetics can depress cardiac conduction;
• patients with advanced stage liver disease or severe renal impairment;
• patients in advanced pregnancy;
• hypovolemic patients may develop severe and sudden hypotension during intrathecal anesthesia, regardless of the local anesthetic used. Hypotension is normally observed after intrathecal block in adults;
• patients treated with Class III antiarrhythmic drugs (e.g. amiodarone) must be closely monitored and the possibility of ECG monitoring should be considered as effects on the heart may be additive.

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

• Central nervous system block: can cause cardiovascular depression especially in the presence of hypovolemia. Epidural anesthesia should therefore be used with caution in patients with reduced cardiovascular function.
• Retrobulbar injections: can, in very rare cases, reach the cerebral subarachnoid space causing temporary blindness, cardiovascular collapse, apnea, convulsions, etc. Such reactions must be diagnosed and treated immediately.
• Retro and peribulbar injections of local anesthetics: involve 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 these reactions to tissues is related to the extent of trauma, the concentration of local anesthetic and the duration of tissue exposure to the local anesthetic. As with all local anesthetics, it is therefore necessary to use the lowest doses and concentrations that can allow the desired effect to be obtained.

Vasoconstrictors can worsen tissue reactions and should only be used when indicated.
Local anesthetics, even at low doses, injected into the head and neck, as in the performance of stellate ganglion blocks, can produce systemic toxicity due to unintentional intra-arterial injection or intravascular absorption or into the subarachnoid space

• Paracervical block can sometimes cause fetal bradycardia/tachycardia. Therefore, careful monitoring of fetal heart rate is necessary.
• Continuous intra-articular infusion is not an approved indication for Bupivacaina Recordati. However, cases of chondrolysis in patients who received post-operative continuous intra-articular infusion of local anesthetics have been reported, exclusively in North America. The majority of chondrolysis cases reported involved the shoulder joint. No causal relationship has been established.

A rare but serious adverse reaction following spinal anesthesia is total or high spinal block and

consequent cardiovascular and respiratory depression. Cardiovascular depression is caused

by extensive sympathetic block with resulting profound hypotension and bradycardia or even cardiac

arrest. Respiratory depression can be caused by blocking the innervation of the respiratory muscles,

including the diaphragm. The risk of total or high spinal block is greater in elderly patients or in advanced pregnancy. In these patients the dose should therefore be reduced.

The onset of neurological damage is a rare consequence of intrathecal anesthesia and can involve

paresthesia, anesthesia, motor weakness and paralysis. Occasionally such damage is permanent.

Caution is recommended in patients with neurological disorders such as multiple sclerosis, hemiplegia,

paraplegia and neuromuscular disorders, even if it is believed that intrathecal anesthesia does not negatively affect these disorders. Before starting treatment, it is necessary to consider whether

the benefits outweigh the possible risks for the patient.
Epidural anesthesia can cause hypotension and bradycardia. The risk can be reduced by pre-filling the circulation with crystalloid or colloid solutions. Hypotension should be treated immediately with the administration, possibly repeated, of a sympathomimetic intravenously. In children, the dosage must be adjusted according to age and weight.
When bupivacaine is administered intra-articularly, caution is recommended in case of suspected recent major intra-articular trauma or when surgery has produced extensive exposure of the joint as this may accelerate absorption and lead to higher plasma concentrations.
If infiltrations for local anesthesia are performed in areas devoid of collateral circulation possibilities (fingers, root of the penis, etc.) it is a precautionary rule to use the anesthetic without a vasoconstrictor to avoid ischemic necrosis.
Bupivacaina Recordati must be used with absolute caution in subjects treated with MAOI drugs or tricyclic antidepressants.
Before use, the doctor must ascertain the state of the circulatory conditions of the subjects to be treated.
Any overdose of anesthetic must be avoided and two maximum doses of the latter must never be administered without a minimum interval of 24 hours having elapsed.
It is nevertheless necessary to use the lowest doses and concentrations that allow the desired effect to be obtained.
It is advisable to use an adequate dose-test possibly in association with adrenaline, in order to promptly avoid an accidental intravenous or intrathecal injection.
The anesthetic solution must be injected with caution in small doses after about 10 seconds from a preliminary aspiration. Especially when infiltrating highly vascularized areas, it is advisable to wait about 2 minutes before proceeding with the actual loco-regional block.
The patient must be kept under accurate control, immediately suspending administration at the first sign of alarm (e.g. modification of sensorium).
Immediate availability of equipment, medicines and personnel suitable for emergency treatment must be ensured, as rare cases of serious reactions, sometimes with a fatal outcome, have been reported following the use of local anesthetics, even in the absence of individual hypersensitivity in the anamnesis.

Dosage and method of administration
Bupivacaina Recordati is usually used in minimum dosages, varying according to the indications, from 2-3
mg to 100-150 mg, as indicated as a guideline in the table.
The solubility of bupivacaine at a pH higher than 6.5 is limited. This must be taken into consideration when
adding alkaline solutions, such as carbonates, which may cause the solution to precipitate.
The solutions do not contain preservatives, are for single use only and must be used immediately
after opening. Any residual drug must be discarded.
The vials of Bupivacaina Recordati must not be resterilized.
The maximum dosage for an adult and for single administration should not exceed 150 mg,
corresponding to 30 ml of the solution; more generally, the safety dose, for both adults and children,
that is advisable not to exceed, is 2 mg/kg for single administration.
In prolonged analgesic therapy, doses ranging from 0.25 to 1 mg/kg of body weight are usually used;
administration can be repeated 2-3 times within 24 hours.
N.B. When performing prolonged blocks for successive bolus administration, the risk of reaching toxic plasma concentrations or inducing neuronal damage
at the local level must be considered.
The dose to be administered must be calculated based on the doctor's experience and knowledge
of the patient's clinical condition. It is necessary to use the lowest doses that can allow to obtain
adequate anesthesia. Individual variations may occur regarding the onset and duration of action. In children with high body weight, a gradual reduction of the
dosage based on ideal body weight is often necessary. Reference texts should be consulted both
regarding the aspects that affect specific block techniques and regarding the individual needs
of the patient. The degree of spread of anesthesia can be difficult to predict but
is influenced by the volume of drug administered, especially with regard to isobaric solutions.
To prevent accidental intravascular injection, aspiration should be performed before and during the
administration of the main dose, which should be injected slowly or in increasing doses. During
the procedure, carefully monitor the patient's vital functions and maintain verbal contact.
If epidural anesthesia is required, it is recommended to precede a test dose of 3-5
ml of bupivacaine with adrenaline. An accidental intravascular injection can be recognized by a
temporary increase in heart rate; an accidental intrathecal injection is recognized by signs
of spinal block. At the first sign of toxicity, immediately stop administration
(see section “Undesirable effects”).

Overdose
Accidental intravascular injection of local anesthetics can cause immediate systemic toxic reactions
(from a few seconds to a few minutes).
In case of overdose, systemic toxicity manifests later (15-60 minutes after injection) and
this is due to a slowed increase in blood concentrations of local anesthetic.

Bupivacaina Recordati hyperbaric, under the recommended conditions of use, is unlikely to promote

blood levels high enough to cause systemic toxicity. However, if other local anesthetics

are administered concurrently, the toxic effects are additive and can cause systemic toxicity.
For the treatment of any overdose, administration must be stopped at the first sign
of alarm, place the patient in a horizontal position and ensure the patency of the airways
by administering oxygen in case of severe dyspnea or performing artificial ventilation (Ambu bag).
The use of bulbous stimulants should be avoided so as not to worsen the situation by increasing oxygen consumption.
Any convulsions can be controlled with the use of diazepam at a dose of 10-20 mg intravenously; barbiturates are instead discouraged as they can exacerbate bulbous depression. The
circulation can be supported with the administration of corticosteroids in appropriate doses via
intravenous route; diluted solutions of alpha-beta-stimulants with vasoconstrictor action may be added
(mefentermine, metaraminol and others) or atropine sulfate. Sodium bicarbonate can be used as an acidifier
in targeted concentration, intravenously.

Possible undesirable effects
The profile of adverse reactions of Bupivacaina Recordati is similar to that of other local anesthetics
with long duration of action. Drug adverse reactions are difficult to distinguish from
physiological effects resulting from nerve conduction block (such as decreased blood pressure,
bradycardia, temporary urinary retention) and events caused directly by the injection
(e.g., nerve fiber trauma, spinal hematoma) or indirectly (e.g., epidural abscess and

meningitis) or events associated with cerebrospinal fluid leakage (e.g., post-dural puncture headache).
The onset of neurological damage is a rare but well-known consequence of regional anesthesia and in
particular, of epidural and spinal anesthesia.

Acute systemic toxicity
Systemic toxic reactions mainly affect the central nervous system and the cardiovascular system. These reactions are caused by high blood concentrations of local anesthetic
following accidental intravascular injection, overdose or exceptionally rapid absorption from
highly vascularized areas. Reactions to the central nervous system are similar to those
of other amidic-type local anesthetics while reactions at the cardiac level depend, both quantitatively and
qualitatively, to a greater extent on the drug.

Bupivacaina Recordati hyperbaric, under the recommended conditions of use, is unlikely to promote

blood levels high enough to cause systemic toxicity. However, if other local anesthetics

are administered concurrently, the toxic effects are additive and can cause systemic toxicity.
Toxicity to the central nervous system manifests gradually, with symptoms and signs of
increasing severity. The first symptoms are, as a rule, paresthesia in the circumoral region, numbness of the
tongue, feeling of emptiness in the head, hyperacusis, tinnitus and visual disturbances. Dysarthria, muscle spasm or
tremor are more serious manifestations and precede the onset of generalized seizures. These
signs should not be confused with erotic behaviors. Unconsciousness and convulsive crises may follow
which can last from a few seconds to several minutes. After the convulsions, due to
increased muscle activity, interference with breathing and the eventual lack of
airway patency, hypoxia and hypercapnia rapidly manifest. In severe cases, apnea may occur. Acidosis, hyperkalemia, hypocalcemia and hypoxia increase and amplify the effects
toxic of local anesthetics.
The return of the patient to the initial clinical conditions is consequent to the redistribution of the anesthetic
local from the central nervous system and subsequent metabolism and excretion. Recovery can be
rapid if large amounts of drug have not been administered.
In severe cases, effects on the cardiovascular system may occur, usually preceded
by signs of central nervous system toxicity. In deeply sedated or undergoing patients
general anesthesia, effects on the cardiovascular system may occur without prodromic effects of the central nervous system. As a result of high systemic concentrations of
local anesthetics, hypotension, bradycardia, arrhythmias and even cardiac arrest can occur, but in
rare cases has cardiac arrest occurred without prodromic effects of the central nervous system.
In children, it may be difficult to detect the onset of early signs of local anesthetic systemic toxicity when the block is administered during general anesthesia.

Treatment of acute systemic toxicity
The administration of the anesthetic must be stopped immediately if signs of
acute systemic toxicity or total spinal blockappear. Symptoms of central nervous system toxicity
(convulsions, depression of the central nervous system) must be treated immediately with an
adequate support of airway patency and breathing and with the administration of
anticonvulsants, such as diazepam at a dose of 10-20 mg intravenously; barbiturates are instead discouraged as they can exacerbate bulbous depression. The circulation can be supported with the
administration of corticosteroids in appropriate doses via
intravenous route; diluted solutions of alpha-beta-stimulants with vasoconstrictor action may be added
(mefentermine, metaraminol and others) or atropine sulfate.
If circulatory arrest occurs, immediate cardiopulmonary resuscitation must be performed. It is of vital importance to ensure optimal oxygenation, support ventilation
and circulation and treat acidosis.
If cardiovascular depression occurs (hypotension, bradycardia), adequate treatment should be considered with fluids intravenously, vasopressors and/or inotropes.
In children, the dosage must be adjusted to age and weight.
If cardiac arrest occurs, it may be necessary to prolong resuscitation maneuvers
to achieve a favorable outcome.

Note: italicized parts of the text relate only to the hyperbaric formulation