Bupivacaine

Bupivacaine is a long-acting amide local anaesthetic used for infiltration, nerve blocks, epidural analgesia and spinal anaesthesia. It has the greatest cardiotoxicity among the common amide agents, and the 0.75% concentration is contraindicated for obstetric epidural use. Its long duration makes it the usual agent for postoperative and labour analgesia.

Class. Amide local anaesthetic (long-acting).

Mechanism. Reversible blockade of voltage-gated sodium channels. It binds tightly and dissociates slowly from cardiac sodium channels, which explains severe, resistant arrhythmias after overdose.

Pharmacokinetics. Onset 5 to 15 minutes (infiltration, block), 5 to 10 minutes (spinal). Duration 3 to 8 hours depending on concentration and site. Protein binding 95% (alpha-1 acid glycoprotein). Half-life about 3 hours in adults, longer in neonates. Hepatic metabolism (CYP3A4) to pipecolylxylidine, renal excretion.

Indications are surgical anaesthesia (spinal, epidural, blocks), postoperative analgesia, labour analgesia, and diagnostic and therapeutic nerve blocks.

Maximum doses (adults)

• Plain: 2 mg/kg, not above 150 mg (some labels allow 175 mg), and 400 mg in 24 hours.
• With adrenaline: some labels allow up to 225 mg. Reduce in older adults, hepatic impairment and heart failure.
• Concentrations: 0.25% is 2.5 mg/mL, 0.5% is 5 mg/mL and 0.75% is 7.5 mg/mL.

Techniques

• Infiltration: 0.25 to 0.5%, up to the maximum dose.
• Peripheral nerve block: 0.25 to 0.5% in 20 to 30 mL (50 to 150 mg).
• Epidural, surgical: 0.5% in 10 to 20 mL (50 to 100 mg) in incremental doses after a test dose; 0.75% for non-obstetric surgery only.
• Epidural labour analgesia: loading dose 0.1 to 0.25% in 8 to 15 mL; maintenance infusion 0.0625 to 0.125% at 8 to 15 mL/hour with fentanyl 2 micrograms/mL, or intermittent boluses.
• Spinal (hyperbaric 0.5% with glucose): 10 to 15 mg (2 to 3 mL) for lower limb and abdominal surgery; 10 to 12.5 mg with an opioid for caesarean section; reduce in older adults and pregnancy.
• Spinal (isobaric 0.5%): 10 to 20 mg.
• Postoperative epidural infusion: 0.1% to 0.125% at 4 to 12 mL/hour with an opioid, titrated.
• Intravenous regional anaesthesia (Bier block): contraindicated because of cardiac arrest when the tourniquet is released.

Children. Maximum 2 mg/kg. Caudal block: 0.25% at 0.5 to 1 mL/kg (1.25 to 2.5 mg/kg) depending on level; 2 mg/kg ceiling still applies. Infusions in infants (under 6 months) limited to 0.2 mg/kg/hour to avoid accumulation.

Contraindications. Hypersensitivity to amide anaesthetics; intravenous regional anaesthesia; obstetric paracervical block; 0.75% concentration for obstetric epidural anaesthesia; infection at the injection site; coagulopathy or anticoagulation for neuraxial techniques; hypovolaemia (relative for spinal and epidural).

Boxed-warning-level risks. Cardiac arrest with difficult resuscitation after 0.75% in obstetric epidural; severe, resistant cardiotoxicity with inadvertent intravascular injection; seizures and cardiovascular collapse from systemic toxicity.

Adverse effects. Common: hypotension and bradycardia (spinal, epidural), nausea, motor block lasting longer than desired, urinary retention. Serious: local anaesthetic systemic toxicity, high or total spinal block, cauda equina injury, nerve injury, arrhythmias and cardiac arrest, anaphylaxis (rare).

Interactions. CYP3A4 inhibitors (azoles, macrolides, ritonavir) increase levels. Other local anaesthetics add systemic toxicity. Beta blockers and calcium channel blockers add cardiac depression. Anticoagulants affect timing of neuraxial blocks. Epidural opioids enhance analgesia and add respiratory depression.

Common prescribing errors. Using 0.75% in obstetrics; exceeding 2 mg/kg when combining techniques; confusing hyperbaric and isobaric preparations; giving a spinal dose by epidural or the reverse; mixing up bupivacaine with liposomal formulations (different doses); injection without aspiration or incremental dosing.

Special groups

• Pregnancy: used for labour and caesarean section with reduced spinal doses; avoid 0.75% epidural and paracervical use.
• Breastfeeding: compatible.
• Older adults: reduce spinal and epidural doses by 20 to 30%.
• Kidney impairment: no adjustment for single doses.
• Liver impairment: reduce repeated dose and infusion; avoid prolonged infusion in severe disease.
• Regional: confirm baricity and concentration on ampoules before drawing up, and keep spinal preparations separate from those for infiltration.

Formulations. Plain solution 0.25, 0.5 and 0.75%; with adrenaline (1 in 200,000); hyperbaric 0.5% with 8% glucose for spinal use; epidural infusion bags.

Administration. Aspirate before each injection and inject in 3 to 5 mL increments with pauses. A test dose with adrenaline (3 mL of 1.5% lidocaine with 1 in 200,000 adrenaline) is used by many for epidural catheters. Do not use in the presence of local infection.

Baseline. Allergy history, coagulation, platelet count, anticoagulant timing, spinal anatomy, liver function and cardiac status. Have intravenous access, resuscitation equipment and lipid emulsion ready before any block.

Monitoring. Continuous electrocardiogram, blood pressure and oxygen saturation during and for at least 30 minutes after block. Sensory level and motor block checks. Epidural infusions: check every 1 to 4 hours for level, motor block and signs of toxicity or haematoma.

Therapeutic drug monitoring. Not used routinely.

Dose reduction and stopping thresholds. Stop injection or infusion at any sign of toxicity, high block, new neurological deficit or severe back pain. Reduce infusion rate for dense motor block.

Referral and escalation. Seizures or collapse after injection: stop the injection, give oxygen and airway support, benzodiazepine for seizures, and 20% lipid emulsion 1.5 mL/kg over 1 minute then 15 mL/kg/hour (repeat the bolus up to twice and double the infusion rate if collapse persists; maximum cumulative 12 mL/kg). Use reduced adrenaline doses (1 microgram/kg or less) in arrest. New leg weakness after an epidural infusion needs urgent imaging for haematoma.