Drugs List

Therapeutic Indications

Uses

Local anaesthetic for percutaneous infiltration

Local anaesthetic for peripheral nerve block

Local anaesthetic for central nerve block (caudal or epidural)


Bupivacaine with adrenaline is for specialist use where prolonged anaesthesia is required.

As sensory nerve block is more marked than motor nerve block, bupivacaine is especially useful in the relief of pain, e.g. during labour.

Administration

For local, perineural, epidural, and caudal injection.

Careful aspiration before injection is recommended to prevent intravascular administration.

A test dose of 3 to 5ml bupivacaine with adrenaline should be used in epidural anaesthesia, an accidental intravascular injection will be recognised by an increase in heart rate. The patient's heart rate should be repeatedly measured and verbal contact maintained for 5 minutes following this test dose.

The dose of bupivacaine should be injected slowly (25 to 50mg/min) in incremental doses.

The patient's vital signs should be observed closely during the injection and verbal contact maintained. If toxic symptoms occur, the injection should be stopped immediately.

Handling

For single use only - any unused solution should be discarded.

The solution must not be stored in contact with metals (e.g. needles or metal parts of syringes) as dissolved metal ions may cause swelling at the injection site.

Incompatibilities

Contraindications

Thyrotoxicosis

Severe cardiac disease (especially when tachycardia present)

Epidural anaesthesia is contraindicated in:
Active central nervous system disease
Meningitis
Poliomyelitis
Intracranial haemorrhage
Subacute degeneration of the cord due to pernicious anaemia
CNS tumours
Tuberculosis of spine
Cardiogenic shock
Hypovolaemic shock
Coagulation abnormalities
Concurrent anticoagulant therapy
Expanding cerebral lesion, a tumour, cyst or abscess which may obstruct cerebrospinal fluid or blood circulation if the intracranial pressure is suddenly altered.

Bupivacaine must not be used for intravenous regional anaesthesia (Bier's block).

Bupivacaine with adrenaline should not be administered in areas of the body supplied by end arteries or areas with a compromised blood supply such as digits, nose, external ear, penis, etc.

Precautions and Warnings

Bupivacaine should only be used by those with the necessary training and experience.

Not to be injected into inflamed or infected tissues. Septicaemia can increase the risk of post operative intraspinal abscess formation.

The patients vital signs should be observed closely during the injection and verbal contact maintained. If toxic symptoms occur, the injection should be stopped immediately.

Cardiac arrest with difficult resuscitation or death has occurred when bupivacaine has been used for epidural anaesthesia in obstetric patients.

Resuscitation facilities should be available. Intravenous access for resuscitation purposes should be established before bupivacaine with adrenaline is administered.

Repeated doses may cause significant increases in blood levels with each dose due to the slow accumulation of bupivacaine.

Tolerance varies with the status of the patient. Young, debilitated, elderly or acutely ill patients should be given reduced doses depending on their physical status.

Allergic reactions, including anaphylactic shock, have occurred rarely. Bupivacaine and adrenaline solution contains sodium metabisulfite which can cause allergic reactions including anaphylaxis or asthmatic episodes in susceptible individuals.

Solutions containing adrenaline should be used with caution in patients with:
Hyperthyroidism
Diabetes
Phaeochromocytoma
Narrow angle glaucoma
Hypokalaemia
Hypercalcaemia
Severe renal impairment
Prostatic adenoma leading to residual urine
Cerebrovascular disease
Organic brain damage

Bupivacaine may cause acute toxicity effects on the central nervous and cardiovascular systems if its use results in high plasma concentrations of the drug.

Bupivacaine with adrenaline should be used with caution when used for epidural anaesthesia in patients with impaired cardiovascular function including:
Arteriosclerosis
Heart disease
Cardiac dilation (severe angina pectoris, obstructive cardiomyopathy, hypertension
Arrhythmias
History of recent myocardial infarction
Myocardial degeneration
Hypotension below 90mm systolic or less than 30% of their average systolic blood pressure
Gross hypertension
As they may have a decreased ability to respond to dilatation of the vascular bed and they may be be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by bupivacaine.

Epidural anaesthesia can lead to hypotension and bradycardia. Precautions against these effects should be taken and may include pre-loading the circulation with crystalloid or colloid solution. If hypotension occurs, it should be treated appropriately. Marked hypotension should be avoided in patients with cardiac decompensation.
Severe hypotension may result from hypovolaemia due to haemorrhage or dehydration, or from aorto-caval occlusion in patients with massive ascites, large abdominal tumours or late pregnancy.

Use with caution in patients with hepatic disease or with reduced hepatic blood flow as bupivacaine is metabolised by the liver.

Dosage for epidural anaesthesia should be reduced in patients with impaired respiratory function. Patients with a splinted diaphragm which interferes with breathing such as those with hydramnios, large ovarian or uterine tumours, pregnancy, ascites or omental obesity are at risk of hypoxia due to respiratory inadequacy. Lateral tilt, oxygen and mechanical ventilation should be used when indicated. Dosage should be reduced in such patients.

Epidural anaesthesia should be produced with caution in patients with:
Hypovolaemia as sudden and severe hypotension can develop during epidural anaesthesia.
Dehydration
Obesity
Senility
Cerebral atheroma
Toxaemia

Epidural anaesthesia can cause intercostal paralysis at high levels. This can lead to hypoxia in patients who are breathless for any reason including pleural effusion.

There have been reports of respiratory arrest following retrobulbar blocks. Necessary equipment, drugs and personnel should be immediately available prior to retrobulbar block.

Local anaesthetics should be given with great caution if at all to patients with pre-existing abnormal neurological conditions, e.g. myasthenia gravis or epilepsy.

Pregnancy - see Pregnancy section

Patients must wait for the effects of bupivacaine or other drugs administered (such as sedatives or other CNS depressant drugs) to clear before driving, machinery operation or other skilled tasks are attempted.

Pregnancy and Lactation

Pregnancy

Bupivacaine should not be administered in early pregnancy unless the benefits outweigh the risks.

Paracervical nerve block may cause foetal bradycardia. Labour may be prolonged so that caesarian section is required. There may be greater adverse effects on the foetus following paracervical blocks compared to other nerve blocks used in obstetrics. Paracervical blocks should be undertaken with special care due to the systemic toxicity of bupivacaine.

There is no evidence of untoward effects of bupivacaine in human pregnancy. Decreased pup survival in rats and an embryological effect in rabbits has been observed when large doses were administered.

Adrenaline is teratogenic in some animal species, however human teratogenicity has not been studied. Adrenaline crosses the placenta and may reduce placental blood flow. Schaefer comments that the systemic use of adrenaline is restricted to emergency.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Bupivacaine enters human breast milk, but the quantities are so small and it is not orally absorbed so that there is no risk to the child at therapeutic dose levels.

Adrenaline has poor oral bioavailability and a short half life, any adrenaline in milk is considered unlikely to affect a breastfed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Hypersensitivity reactions
Allergic reaction
Anaphylactic shock
Paraesthesia
Dizziness
CNS effects
Convulsions
Excitation
Depression
Drowsiness
Tongue numbness
Hyperacusis
Visual disturbances
Unconsciousness
Coma
Tremor
Light-headedness
Tinnitus
Dysarthria
Muscle twitch
Neuropathy
Nerve damage
Arachnoiditis
Paresis
Paraplegia
Diplopia
Blurred vision
Bradycardia
Cardiac arrest
Arrhythmias
Hypotension
Hypertension
Respiratory depression
Nausea
Vomiting
Urinary retention
Hypoxia
Apnoea
Acidosis
Hyperkalaemia
Respiratory arrest
Localised areas of paraesthesia
Localised areas of anaesthesia
Muscle weakness
Loss of sphincter control
Hepatic impairment

Presentation

Solution for injection containing bupivacaine hydrochloride 26.375mg/10ml, equivalent to bupivacaine hydrochloride anhydrous 25mg/10ml (0.5%) and adrenaline acid tartrate 0.091mg/10ml, equivalent to adrenaline 0.05mg/10ml.

Solution for injection containing bupivacaine hydrochloride 52.75mg/10ml, equivalent to bupivacaine hydrochloride anhydrous 50mg/10ml (0.5%) and adrenaline acid tartrate 0.091mg/10ml, equivalent to adrenaline 0.05mg/10ml.

Drugs List

Therapeutic Indications

Uses

Local anaesthetic for percutaneous infiltration

Local anaesthetic for peripheral nerve block

Local anaesthetic for central nerve block (caudal or epidural)


Bupivacaine with adrenaline is for specialist use where prolonged anaesthesia is required.

As sensory nerve block is more marked than motor nerve block, bupivacaine is especially useful in the relief of pain, e.g. during labour.

Dosage

Bupivacaine with adrenaline should only be used by those with the necessary training and experience.

Dosage varies and depends on the area to be anaesthetised, the vascularity of the tissues, the number of neuronal segments to be blocked, the individual tolerance and the technique used. The maximum dose must be determined by evaluating the size and physical status of the patient, including age, weight, physique and clinical condition. The usual rate of systemic absorption from a particular injection site should be considered.

To avoid excessive dosage in obese patients, dose may need to be calculated on the basis of ideal body weight.

The lowest dose needed to provide effective anaesthesia should be administered. A single dose is usually sufficient for most indications.

Bupivacaine may take up to 30 minutes to produce the full effect.

The doses stated may not be appropriate in some settings and expert advice should be sought.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For local, perineural, epidural, and caudal injection.

Careful aspiration before injection is recommended to prevent intravascular administration.

A test dose of 3 to 5ml bupivacaine with adrenaline should be used in epidural anaesthesia, an accidental intravascular injection will be recognised by an increase in heart rate. The patient's heart rate should be repeatedly measured and verbal contact maintained for 5 minutes following this test dose.

The dose of bupivacaine should be injected slowly (25 to 50mg/min) in incremental doses.

The patient's vital signs should be observed closely during the injection and verbal contact maintained. If toxic symptoms occur, the injection should be stopped immediately.

Handling

For single use only - any unused solution should be discarded.

The solution must not be stored in contact with metals (e.g. needles or metal parts of syringes) as dissolved metal ions may cause swelling at the injection site.

Incompatibilities

Contraindications

Thyrotoxicosis

Severe cardiac disease (especially when tachycardia present)

Epidural anaesthesia is contraindicated in:
Active central nervous system disease
Meningitis
Poliomyelitis
Intracranial haemorrhage
Subacute degeneration of the cord due to pernicious anaemia
CNS tumours
Tuberculosis of spine
Cardiogenic shock
Hypovolaemic shock
Coagulation abnormalities
Concurrent anticoagulant therapy
Expanding cerebral lesion, a tumour, cyst or abscess which may obstruct cerebrospinal fluid or blood circulation if the intracranial pressure is suddenly altered.

Bupivacaine must not be used for intravenous regional anaesthesia (Bier's block).

Bupivacaine with adrenaline should not be administered in areas of the body supplied by end arteries or areas with a compromised blood supply such as digits, nose, external ear, penis, etc.

Precautions and Warnings

Bupivacaine should only be used by those with the necessary training and experience.

Not to be injected into inflamed or infected tissues. Septicaemia can increase the risk of post operative intraspinal abscess formation.

The patients vital signs should be observed closely during the injection and verbal contact maintained. If toxic symptoms occur, the injection should be stopped immediately.

Cardiac arrest with difficult resuscitation or death has occurred when bupivacaine has been used for epidural anaesthesia in obstetric patients.

Resuscitation facilities should be available. Intravenous access for resuscitation purposes should be established before bupivacaine with adrenaline is administered.

Repeated doses may cause significant increases in blood levels with each dose due to the slow accumulation of bupivacaine.

Tolerance varies with the status of the patient. Young, debilitated, elderly or acutely ill patients should be given reduced doses depending on their physical status.

Allergic reactions, including anaphylactic shock, have occurred rarely. Bupivacaine and adrenaline solution contains sodium metabisulfite which can cause allergic reactions including anaphylaxis or asthmatic episodes in susceptible individuals.

Solutions containing adrenaline should be used with caution in patients with:
Hyperthyroidism
Diabetes
Phaeochromocytoma
Narrow angle glaucoma
Hypokalaemia
Hypercalcaemia
Severe renal impairment
Prostatic adenoma leading to residual urine
Cerebrovascular disease
Organic brain damage

Bupivacaine may cause acute toxicity effects on the central nervous and cardiovascular systems if its use results in high plasma concentrations of the drug.

Bupivacaine with adrenaline should be used with caution when used for epidural anaesthesia in patients with impaired cardiovascular function including:
Arteriosclerosis
Heart disease
Cardiac dilation (severe angina pectoris, obstructive cardiomyopathy, hypertension
Arrhythmias
History of recent myocardial infarction
Myocardial degeneration
Hypotension below 90mm systolic or less than 30% of their average systolic blood pressure
Gross hypertension
As they may have a decreased ability to respond to dilatation of the vascular bed and they may be be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by bupivacaine.

Epidural anaesthesia can lead to hypotension and bradycardia. Precautions against these effects should be taken and may include pre-loading the circulation with crystalloid or colloid solution. If hypotension occurs, it should be treated appropriately. Marked hypotension should be avoided in patients with cardiac decompensation.
Severe hypotension may result from hypovolaemia due to haemorrhage or dehydration, or from aorto-caval occlusion in patients with massive ascites, large abdominal tumours or late pregnancy.

Use with caution in patients with hepatic disease or with reduced hepatic blood flow as bupivacaine is metabolised by the liver.

Dosage for epidural anaesthesia should be reduced in patients with impaired respiratory function. Patients with a splinted diaphragm which interferes with breathing such as those with hydramnios, large ovarian or uterine tumours, pregnancy, ascites or omental obesity are at risk of hypoxia due to respiratory inadequacy. Lateral tilt, oxygen and mechanical ventilation should be used when indicated. Dosage should be reduced in such patients.

Epidural anaesthesia should be produced with caution in patients with:
Hypovolaemia as sudden and severe hypotension can develop during epidural anaesthesia.
Dehydration
Obesity
Senility
Cerebral atheroma
Toxaemia

Epidural anaesthesia can cause intercostal paralysis at high levels. This can lead to hypoxia in patients who are breathless for any reason including pleural effusion.

There have been reports of respiratory arrest following retrobulbar blocks. Necessary equipment, drugs and personnel should be immediately available prior to retrobulbar block.

Local anaesthetics should be given with great caution if at all to patients with pre-existing abnormal neurological conditions, e.g. myasthenia gravis or epilepsy.

Pregnancy - see Pregnancy section

Patients must wait for the effects of bupivacaine or other drugs administered (such as sedatives or other CNS depressant drugs) to clear before driving, machinery operation or other skilled tasks are attempted.

Pregnancy and Lactation

Pregnancy

Bupivacaine should not be administered in early pregnancy unless the benefits outweigh the risks.

Paracervical nerve block may cause foetal bradycardia. Labour may be prolonged so that caesarian section is required. There may be greater adverse effects on the foetus following paracervical blocks compared to other nerve blocks used in obstetrics. Paracervical blocks should be undertaken with special care due to the systemic toxicity of bupivacaine.

There is no evidence of untoward effects of bupivacaine in human pregnancy. Decreased pup survival in rats and an embryological effect in rabbits has been observed when large doses were administered.

Adrenaline is teratogenic in some animal species, however human teratogenicity has not been studied. Adrenaline crosses the placenta and may reduce placental blood flow. Schaefer comments that the systemic use of adrenaline is restricted to emergency.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Bupivacaine enters human breast milk, but the quantities are so small and it is not orally absorbed so that there is no risk to the child at therapeutic dose levels.

Adrenaline has poor oral bioavailability and a short half life, any adrenaline in milk is considered unlikely to affect a breastfed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Hypersensitivity reactions
Allergic reaction
Anaphylactic shock
Paraesthesia
Dizziness
CNS effects
Convulsions
Excitation
Depression
Drowsiness
Tongue numbness
Hyperacusis
Visual disturbances
Unconsciousness
Coma
Tremor
Light-headedness
Tinnitus
Dysarthria
Muscle twitch
Neuropathy
Nerve damage
Arachnoiditis
Paresis
Paraplegia
Diplopia
Blurred vision
Bradycardia
Cardiac arrest
Arrhythmias
Hypotension
Hypertension
Respiratory depression
Nausea
Vomiting
Urinary retention
Hypoxia
Apnoea
Acidosis
Hyperkalaemia
Respiratory arrest
Localised areas of paraesthesia
Localised areas of anaesthesia
Muscle weakness
Loss of sphincter control
Hepatic impairment

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store below 25 degrees C
Keep container in outer carton

Reference Sources

British National Formulary, 62nd Edition (2011) Pharmaceutical Press, London.

BNF for Children (2011-2012) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Bupivacaine and adrenaline injection 0.25%. Goldshield Group Limited. Revised July 2011
Summary of Product Characteristics: Bupivacaine and adrenaline injection 0.5%. Goldshield Group Limited. Revised July 2011

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Bupivacaine Last revised: February 28, 2011
Last accessed: February 20, 2012

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Epinephrine Last revised: September 29, 2009
Last accessed: February 20, 2012