Long acting local anesthetic injection for spinal anesthesia

Each ml Injection contains:
Active ingredient:
Bupivacaine HCI monohydrate equivalent to
Bupivacaine HCI anhydrous 5 mg
Dextrose monohydrate 80 mg

Bupivacaine is a long acting local anesthetic agent of the amide type. Bupivacaine spinal heavy has rapid onset of action and long duration. The duration of analgesia In the T10 - T12 segments is 2-3 hours. Bupivacaine spinal heavy produces a moderate muscular relaxation of the lower extremities lasting 2-2.5 hours. The motor blockade of the abdominal muscles makes the solution suitable for performance of abdominal surgery lasting for 45-60 minutes. The duration of motor blockade does not exceed the duration of analgesia.
Bupivacaine spinal heavy is hyperbaric and its initial spread in the subarachnoid space is considerable affected by gravity. Moreover, it spreads cephalad more extensively than the isobaric solutions, even in the horizontal position when the effect of gravity is minimal. Due to the larger intrathecal distribution and the consequently lower mean concentration the duration of anesthesia tends to be shorter. Thus the solution without added dextrose produce a lower level of block, but of longer duration, than the hyperbaric solution. Bupivacaine, like other local anesthetic, causes a reversible blockade of impulse propagation along nerve fibres by preventing the inward movement of sodium ions through the nerve membrane. Local anesthetics of the amide type are thought to act within the sodium channels of the nerve membrane.

- Intrathecal (subarachnoid, spinal) anesthesia for surgical.
- Abdominal surgery lasting 45-60 minutes (including Caesarean section).
- Urological and lower limb surgery lasting 2-3 hours (including hip surgery)

- Known hypersensitivity to local anesthetic of the amide type.
- Acute active diseases of the central nervous system, such as meningitis, poliomyelitis, intracranial haemorrhage and demyelinating, increased intracranial pressure, cerebral and spinal tumors.
- Spinal stenosis and active disease (e.g., spondylitis, tumor) or recent trauma (e.g.. fracture) in the vertebral column.
- Tuberculosis of the spine.
- Pyrogenic infection of the skin at or adjacent to the site of lumbar puncture.
- Septicaemia.
- Pernicious anemia with subacute combined degeneration of the spinal cord.
- Coagulation disorders or ongoing anti-coagulation treatment.
- Uncorrected hypotension, cardiogenic or hypovolemic shock.
- Obstetric paracervical block, intravenous regional anesthesia (Bier's block) and all intravenous infusions.

Dosage and administration:
- The doses recommended below should be regarded as a guide for use in the average adult. Spinal anesthesia for surgery: 1.5-3 ml (7.5-15 mg bupivacaine hydrochloride).
- The dosage in the table are those thought to be necessary for the production of a successful block and should be regarded as guideline for use in the average adult. Regarding spread and duration times, there are wide individual variations and it is impossible to be precise.
- The spread of anesthesia is dependent of several factors including the volume of solution and the position of the patient during and following injection. When injected at the L3-L4 intervertebral space, with patient in the sitting position, 3 ml of bupivacaine spinal heavy spreads to the T7-T10 spinal segments. With the patient receiving the injection in the horizontal position and then turned supine, the blockade spreads to T4-T7 spinal segments. It should be understood that the level of spinal anesthesia achieved with any local anesthetic can be unpredictable in a given patient.
- Bupivacaine spinal heavy may be used in children. One of the differences between small children and adults is a relatively high cerebrospinal fluid (CSF) volume in infants and neonates, requiring a relatively larger dose/kg to produce the same level of block as compared to adult.
The following doses are recommended:
0.40-0.50 mg/kg for infants up to 5 kg.
0.30-0.40 mg/kg for children weighing between 5 and 15 kg.
0.25-0.30 mg/kg for children weighing more than 15 kg.
- Spinal injections should only be made after the subarachnoid space has been clearly identified by lumbar puncture. No drug should be injected until clear cerebrospinal fluid (CSF) is seen to escape from the spinal needle or it is detected by aspiration.
- The solution should be used immediately after opening the ampoule. Any remaining solution should be discarded.

Adverse effects:
- In general, almost all the side effects seen with spinal anesthesia are due to the nerve blockade itself and not to the drug used. This effects include hypotension, bradycardia and post dural puncture headache.
- High or total spinal blockade. Severe adverse reactions following spinal anesthesia are rare but may occur in connection with extensive (total) spinal blockade. Total spinal blockade will result in cardiovascular and respiratory depression. The cardiovascular depression is caused by an extensive sympathetic blockade which may result in profound hypotension and bradycardia, or even cardiac arrest. Ventilatory depression is caused by blockade of the innervation of the respiratory muscles, including the diaphragm.
- Neurological reactions. Neurological damage is rare, though recognised, consequence of regional and particularly spinal anesthesia. It may be due to several causes, such as direct injury to the spinal cord or spinal nerves, anterior spinal artery syndrome, injection of an irritant substance, injection of a non sterile solution or the development of a space occupying lesion (haematoma or abscess) within the spinal canal. These may result in localised areas of paraesthesia or anesthesia, motor weakness, loss of sphincter control and paraplegia. Occasionally these are permanent. Neurological complications of this type have been reported with all local anesthetics used for spinal anesthesia.
- Allergic reactions. Alergy to amide type local anesthetics is very rare but may be present as allergic dermatitis, bronchospasm or anaphylaxis.
Acute systemic toxicily. Like all local anesthetic drugs, bupivacaine may have acute toxic effects on the central nervous and cardiovascular systems, if given in high doses. The first manifestation of CNS toxicity is drowsiness merging into unconsciousness and respiratory arrest. The cardiovascular reactions are depressant and may be characterised by hypotension, myocardial depression, bradycardia and possibly cardiac arrest. In view of the low dosage employed, systemic adverse reactions are rarely associated with spinal anesthesia, but may occur after accidental intravascular injection. Systemic adverse reactions are characterised by numbness of the tongue, light-headedness, dizziness and tremors, followed by convulsions and cardiovascular disorders.

Warnings and precautions:
- The safety and effectiveness of bupivacaine depend on proper dosage, correct technique and adequate precautions. Standard textbooks should be consulted for specific techniques and precautions for spinal anesthetic procedures. If signs of acute systemic toxicity or total spinal block appear, injection of the local anesthetic should be stopped immediately.
- Injection should always be made slowly with frequent aspirations to avoid inadvertent intravascular injection which can produce toxic effects.
- Bupivacaine should be used with caution in patient with cardiac block, impaired liver function and cardiovascular disturbances.
- Bupivacaine should be used with caution during pregnancy and lactation.
- Besides the direct anesthetic effect, local anesthetics may have a very mild effect on mental function and coordination even in the absence of overt CNS toxicity and may temporarily impair locomotion and alertness.
- When any local anesthetic agent is used, resuscitative equipment and agents, including oxygen, should be Immediately available in order to manage possible adverse reactions involving the cardiovascular, respiratory or central nervous systems.
- Spinal anesthesia can cause intercostal paralysis and patients with pleural effusions may suffer respiratory embarrassment.
- Bupivacaine may react with certain metals causing the release of ions into solution. Prolonged contact with metal surfaces should be avoided including metal syringe components.
- The possibility of hypotension and bradycardia following epidural or subarachnoid blockade should be anticipated and appropriate precautions taken, including the prior establishment of an Intravenous line and the availability of vasopressor agents and oxygen. Hypotension is common in patients with hypovolemia due to haemorrhage or dehydration and in those with aortocaval occlusion due to abdominal tumors or the pregnant uterus in late pregnancy. Hypotension is poorly tolerated by patients with coronary or cerebrovascular disease.
- Bupivacaine should be use with caution in patients with genetic predisposition to malignant hyperthermia as the safety of amide local anesthetic agents in these patients has not been fully established A standard protocol for the management of malignant hyperthermia should be available.
- Spinal anesthesia can be unpredictable and very high blocks are sometimes encountered with paralysis of the intercostal muscles, and even the diaphragm, especially in pregnancy. On rare occasions it will be necessary to assist or control ventilation.
- There is an increased risk for high or total spinal blockade in the elderly and in patients in the late stages of pregnancy. The close should therefore be reduced in these patients.

Drug interactions:
- Bupivacaine should be used with care in patients receiving antiarrhythmic drugs with local anesthetic activity or other local anesthetics, as their toxic effects may be additive.
- Increased risk of bupivacaine hydrochloride toxicity with propanolol.

Bupivacaine spinal heavy used as recommended are not likely to cause blood levels high enough to cause systemic toxicity. However, if other local anesthetics are concomitantly administered, toxic effects are additive and may cause systemic toxic reactions.
Toxic symptoms may present following a seemingly normal dose as there is a wide variation in patient response to bupivacaine. Systemic toxicity is initially manifested as CNS excitation e.g., yawning, restlessness, excitement, nervousness, blurred vision, nausea and vomiting, muscle twitching and in more severe cases, convulsions. Excitation may be followed by CNS depression with drowsiness, respiratory failure, coma, cardiac arrhythmias and cardiac arrest.

Treatment of overdosage:
Treatment of a patient with toxic manifestations consists of ensuring adequate ventilation and arresting convulsions. Assisted or controlled ventilation should be maintained with oxygen, if required.
If convulsions occur, intravenous diazepam should be administered incrementally. Sodium thiopentone (5 mg/kg) may be used if diazepam is unavailable or ineffective. If convulsions interfere with breathing and/or are not rapidly controlled by specific anticonvulsant medication, suxamethonium (1-2 mg/kg) may be used to paralyse the patient. Artificial ventilation must then be instituted. If ventricular fibrillation or cardiac arrest occurs, effective cardiovascular resuscitation treatment must be instituted and maintained for a prolonged period if necessary.

Presentation and registration number:
Box, 5 ampoules L 4 ml; GKL1305047143A1



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