Drugs List

Therapeutic Indications

Uses

Local anaesthetic for lumbar epidural block to relieve pain during labour
Treatment of post-operative pain

Administration

For continuous epidural infusion.

To avoid accidental intravascular administration, aspiration is required prior to administering the test dose, loading dose and initiating the infusion.

During administration of the test dose, maintain verbal contact with the patient and monitor heart rate (via an ECG). Stop the infusion immediately if signs of toxicity or intrathecal blockade occur.

Following initiation of the infusion, monitor the patient continuously including assessment of blood pressure, pulse rate, pain management and sedation. Segmental testing of the block is required at least every 2 hours alongside appropriate monitoring for signs of progressive spread or increasing density of the block.

Contraindications

Administration site infection
Children under 18 years
Hypovolaemic shock
Meningitis
Arteriovenous malformation in the vertebral column
Cardiogenic shock
Central nervous system neoplasm
Coagulopathy
Expanding cerebral lesion
Intracranial haemorrhage
Meningomyelocele
Poliomyelitis
Spina bifida
Subacute combined degeneration of spinal cord due to B12 deficiency
Tuberculosis of spine

Precautions and Warnings

Ascites
Debilitation
Elderly
Septicaemia
Severe obesity
Atrioventricular block
Cardiomyopathy
Circulatory failure
Decompensated cardiac failure
Dehydration
Epileptic disorder
Hepatic impairment
Hypotension
Hypovolaemia
Marked cerebral atherosclerosis
Myasthenia gravis
Pleural disorder
Pregnancy
Respiratory impairment
Severe renal impairment

Consider dose modification in patients with respiratory depression
Epidural use: increased risk of bleeding with concurrent thrombolytics
Septicaemia increases risk of post-op intraspinal abscess formation
Advise ability to drive/operate machinery may be affected by side effects
Aspirate prior to injection to avoid intravascular administration
Discard any unused portion
Discontinue immediately if toxic symptoms occur, especially in epidural use
Do not inject near site of skin infection
Resuscitation facilities must be immediately available
Treatment to be administered by or under supervision of specialist
Monitor vital signs, respiration & cardiac function
May cause anaphylactic / anaphylactoid reactions
Discontinue if an intrathecal blockade occurs
Discontinue if hepatic function deteriorates
Maintain treatment at the lowest effective dose
Reduce dose in debilitated patients
Reduce dose in elderly

Accidental intravascular administration or injection into highly vascular areas (particularly with large infusion volumes) may lead to high plasma concentrations of bupivacaine. This can cause central nervous system or cardiovascular toxicity including ventricular arrhythmias, ventricular fibrillation, sudden cardiovascular collapse and death.

Cardiac arrest has been reported which in some cases did not respond appropriately to resuscitative methods. Adequate resuscitation equipment must be available including established intravenous access in all patients.

Bupivacaine may cause hypotension and bradycardia which can lead to more pronounced physiological effects. The risk of hypotension is greater in patients with hypovolaemia (e.g. due to haemorrhage or dehydration) or aortocaval obstruction (e.g. in patients with massive ascites, large abdominal tumours or during late pregnancy). Avoid bupivacaine in patients with untreated hypovolaemia or significantly impaired venous return. Cases of hypotension or bradycardia should be appropriately managed (e.g. with a vasopressor) and can be minimised by preloading with a crystalloid or colloid infusion.

Consider dose reduction in patients with a splinted diaphragm where this interferes with their breathing. These patients are at an increased risk of hypoxia due to respiratory inadequacy or aortocaval compression and may include pregnant patients or those with hydramnios, large ovarian or uterine tumours, ascites or omental obesity. Lateral tilt, oxygen and mechanical ventilation may be required.

Pregnancy and Lactation

Pregnancy

Bupivacaine infusion is considered safe for use during labour. Caution is advised during other stages of pregnancy.

Bupivacaine is licensed for use as a continuous epidural infusion during labour. Available evidence indicates no untoward effects during human pregnancy although CNS and cardiovascular side effects may be intensified by progesterone. Use during late pregnancy carries an increased risk of hypotension and/or hypoxia due to aortocaval compression.

Animal studies using high doses have shown decreased survival and embryological effects. As such, use during early pregnancy is not recommended by the manufacturer.

Administration via paracervical block is associated with a higher incidence of foetal adverse effects including bradycardia. This is not a licensed route of administration for bupivacaine infusion.

Lactation

Bupivacaine is considered safe for use during breastfeeding.

Bupivacaine is present in human breast milk however quantities are very small and bupivacaine is not orally absorbed. Studies have shown no adverse effects in exposed infants.

Some studies have indicated that use during labour may delay the onset of lactation however evidence is conflicting and likely confounded by other medicines used during this period.

Side Effects

Abscess formation (injection site)
Activation of latent Horner's syndrome
Allergic reaction
Anaphylactic reaction
Anaphylactic shock
Apnoea
Arachnoiditis
Bradycardia
Cardiac arrest
Cardiac arrhythmias
Cardiovascular effects
CNS effects
Convulsions
Diplopia
Dizziness
Dysarthria
Hepatic impairment
Hyperacusis
Hypertension
Hypotension
Increase in alkaline phosphatase
Increases in hepatic enzymes (reversible)
Light-headedness
Localised areas of anaesthesia
Loss of sphincter control
Muscle twitch
Muscle weakness
Myocardial depression
Nausea
Nerve damage
Neurological damage
Neuropathy
Paraesthesia
Paraplegia
Paresis
Respiratory depression
Serum bilirubin increased
Systemic toxicity (if accidental intravascular injection)
Tinnitus
Tongue numbness
Tremor
Unconsciousness
Urinary retention
Ventricular arrhythmias
Ventricular fibrillation
Visual disturbances
Vomiting

Presentation

Infusions of bupivacaine.

Drugs List

Therapeutic Indications

Uses

Local anaesthetic for lumbar epidural block to relieve pain during labour
Treatment of post-operative pain

Dosage

Prior to initiating a continuous infusion of bupivacaine, epidural block must be established with a test and loading dose of local anaesthetic. Adrenaline can be included in the test dose to facilitate early detection of accidental intravascular injection (seen as an increase in heart rate).

The following doses are recommended by the manufacturer for healthy adults. Dose adjustments may be required in overweight patients, the elderly, patients in poor general condition and in those with a splinted diaphragm (See Precautions and Warnings). Consult standard textbooks where necessary.

Dosage should be titrated to meet individual requirements using the lowest effective dose.

Adults

Administration

For continuous epidural infusion.

To avoid accidental intravascular administration, aspiration is required prior to administering the test dose, loading dose and initiating the infusion.

During administration of the test dose, maintain verbal contact with the patient and monitor heart rate (via an ECG). Stop the infusion immediately if signs of toxicity or intrathecal blockade occur.

Following initiation of the infusion, monitor the patient continuously including assessment of blood pressure, pulse rate, pain management and sedation. Segmental testing of the block is required at least every 2 hours alongside appropriate monitoring for signs of progressive spread or increasing density of the block.

Contraindications

Administration site infection
Children under 18 years
Hypovolaemic shock
Meningitis
Arteriovenous malformation in the vertebral column
Cardiogenic shock
Central nervous system neoplasm
Coagulopathy
Expanding cerebral lesion
Intracranial haemorrhage
Meningomyelocele
Poliomyelitis
Spina bifida
Subacute combined degeneration of spinal cord due to B12 deficiency
Tuberculosis of spine

Precautions and Warnings

Ascites
Debilitation
Elderly
Septicaemia
Severe obesity
Atrioventricular block
Cardiomyopathy
Circulatory failure
Decompensated cardiac failure
Dehydration
Epileptic disorder
Hepatic impairment
Hypotension
Hypovolaemia
Marked cerebral atherosclerosis
Myasthenia gravis
Pleural disorder
Pregnancy
Respiratory impairment
Severe renal impairment

Consider dose modification in patients with respiratory depression
Epidural use: increased risk of bleeding with concurrent thrombolytics
Septicaemia increases risk of post-op intraspinal abscess formation
Advise ability to drive/operate machinery may be affected by side effects
Aspirate prior to injection to avoid intravascular administration
Discard any unused portion
Discontinue immediately if toxic symptoms occur, especially in epidural use
Do not inject near site of skin infection
Resuscitation facilities must be immediately available
Treatment to be administered by or under supervision of specialist
Monitor vital signs, respiration & cardiac function
May cause anaphylactic / anaphylactoid reactions
Discontinue if an intrathecal blockade occurs
Discontinue if hepatic function deteriorates
Maintain treatment at the lowest effective dose
Reduce dose in debilitated patients
Reduce dose in elderly

Accidental intravascular administration or injection into highly vascular areas (particularly with large infusion volumes) may lead to high plasma concentrations of bupivacaine. This can cause central nervous system or cardiovascular toxicity including ventricular arrhythmias, ventricular fibrillation, sudden cardiovascular collapse and death.

Cardiac arrest has been reported which in some cases did not respond appropriately to resuscitative methods. Adequate resuscitation equipment must be available including established intravenous access in all patients.

Bupivacaine may cause hypotension and bradycardia which can lead to more pronounced physiological effects. The risk of hypotension is greater in patients with hypovolaemia (e.g. due to haemorrhage or dehydration) or aortocaval obstruction (e.g. in patients with massive ascites, large abdominal tumours or during late pregnancy). Avoid bupivacaine in patients with untreated hypovolaemia or significantly impaired venous return. Cases of hypotension or bradycardia should be appropriately managed (e.g. with a vasopressor) and can be minimised by preloading with a crystalloid or colloid infusion.

Consider dose reduction in patients with a splinted diaphragm where this interferes with their breathing. These patients are at an increased risk of hypoxia due to respiratory inadequacy or aortocaval compression and may include pregnant patients or those with hydramnios, large ovarian or uterine tumours, ascites or omental obesity. Lateral tilt, oxygen and mechanical ventilation may be required.

Pregnancy and Lactation

Pregnancy

Bupivacaine infusion is considered safe for use during labour. Caution is advised during other stages of pregnancy.

Bupivacaine is licensed for use as a continuous epidural infusion during labour. Available evidence indicates no untoward effects during human pregnancy although CNS and cardiovascular side effects may be intensified by progesterone. Use during late pregnancy carries an increased risk of hypotension and/or hypoxia due to aortocaval compression.

Animal studies using high doses have shown decreased survival and embryological effects. As such, use during early pregnancy is not recommended by the manufacturer.

Administration via paracervical block is associated with a higher incidence of foetal adverse effects including bradycardia. This is not a licensed route of administration for bupivacaine infusion.

Lactation

Bupivacaine is considered safe for use during breastfeeding.

Bupivacaine is present in human breast milk however quantities are very small and bupivacaine is not orally absorbed. Studies have shown no adverse effects in exposed infants.

Some studies have indicated that use during labour may delay the onset of lactation however evidence is conflicting and likely confounded by other medicines used during this period.

Side Effects

Abscess formation (injection site)
Activation of latent Horner's syndrome
Allergic reaction
Anaphylactic reaction
Anaphylactic shock
Apnoea
Arachnoiditis
Bradycardia
Cardiac arrest
Cardiac arrhythmias
Cardiovascular effects
CNS effects
Convulsions
Diplopia
Dizziness
Dysarthria
Hepatic impairment
Hyperacusis
Hypertension
Hypotension
Increase in alkaline phosphatase
Increases in hepatic enzymes (reversible)
Light-headedness
Localised areas of anaesthesia
Loss of sphincter control
Muscle twitch
Muscle weakness
Myocardial depression
Nausea
Nerve damage
Neurological damage
Neuropathy
Paraesthesia
Paraplegia
Paresis
Respiratory depression
Serum bilirubin increased
Systemic toxicity (if accidental intravascular injection)
Tinnitus
Tongue numbness
Tremor
Unconsciousness
Urinary retention
Ventricular arrhythmias
Ventricular fibrillation
Visual disturbances
Vomiting

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 ).

Further Information

Last Full Review Date: March 2019

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Bupivacaine Hydrochloride 0.1%w/v Solution for Infusion. Advanz Pharma. Revised August 2012.

Summary of Product Characteristics: Bupivacaine Hydrochloride 0.125%w/v Solution for Infusion. Advanz Pharma. Revised August 2012.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 March 2019

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: 03 December 2018
Last accessed: 05 March 2019