Bupivacaine Hydrochloride

Approved Indications:

• Local or regional anesthesia:
• Infiltration, nerve block, epidural, caudal, and spinal anesthesia.
• Surgical anesthesia:
• For procedures requiring prolonged anesthesia, including orthopedic, abdominal, thoracic, and lower limb surgeries.
• Obstetric anesthesia:
• Epidural block for labor analgesia and cesarean section.
• Postoperative pain management:
• Epidural infusions or nerve blocks to control pain after surgery.

Off-label/Clinically Accepted Uses:

• Chronic pain management via continuous nerve block or infusion.
• Sympathetic nerve blocks in complex regional pain syndrome (CRPS).
• Dental procedures requiring long-duration nerve block.

Routes: Infiltration, peripheral nerve block, epidural, caudal, and spinal injection. Not for IV use.

Adult Dosage:

• Infiltration anesthesia: 0.25%–0.5%, up to 175 mg (single dose), repeat after 3 hours if needed. Max 400 mg/24 hours.
• Epidural block:
• Surgical: 0.5%–0.75%, 10–20 mL.
• Labor analgesia: 0.25%, 6–10 mL every 1.5–2 hours or continuous infusion at 6–10 mL/h.
• Spinal anesthesia: 0.75% heavy solution (with dextrose), 1–4 mL depending on procedure and height of block.

Pediatric Dosage:

• Dosing is based on weight, typically 0.25–0.5 mg/kg per injection for nerve blocks or caudal blocks, not exceeding 2–3 mg/kg total.

Elderly/Special Populations:

• Use lower concentrations and slower injection rates.
• Close monitoring for toxicity in hepatic impairment, cardiovascular disease, or renal impairment.
• Dose adjustment may be required due to reduced clearance.

Bupivacaine is an amide-type local anesthetic that reversibly blocks the generation and conduction of nerve impulses by inhibiting voltage-gated sodium channels in neuronal membranes. By preventing the influx of sodium ions during depolarization, it halts nerve conduction, leading to loss of sensation. Its high lipid solubility and protein binding contribute to a longer duration of action, especially useful for prolonged surgical anesthesia and postoperative pain control.

• Absorption: Systemic absorption depends on the route and vascularity of the site. Epidural and nerve block sites absorb slowly.
• Distribution: Widely distributed; crosses the placenta and blood-brain barrier. Plasma protein binding ~95%.
• Metabolism: Metabolized primarily in the liver by cytochrome P450 enzymes (mainly CYP3A4).
• Excretion: Metabolites excreted mainly via the kidneys.
• Onset of Action:
• Infiltration: 1–10 minutes
• Epidural: 10–20 minutes
• Spinal: 5–8 minutes
• Duration of Action:
• Infiltration: up to 6–8 hours
• Epidural/nerve block: 2–8 hours depending on dose/concentration
• Elimination Half-life: Approx. 2.7 hours (longer in neonates and elderly)

• Pregnancy: Not assigned by FDA under new PLLR rules, but historically classified as Category C. Use with caution during labor and delivery due to risk of fetal bradycardia or CNS depression.
• Lactation: Bupivacaine is excreted in small amounts in breast milk. Generally considered compatible with breastfeeding, but infants should be monitored for adverse effects.

• Class: Local Anesthetic
• Subclass: Amide-type long-acting local anesthetic

• Known hypersensitivity to bupivacaine or other amide-type local anesthetics
• Intravenous regional anesthesia (IVRA) due to risk of cardiac arrest
• Severe hypotension or hypovolemia
• Sepsis or infection at the injection site
• Complete heart block without pacemaker

• Cardiovascular toxicity: Risk of bradycardia, hypotension, arrhythmias, and cardiac arrest especially with IV use or overdose.
• CNS toxicity: Seizures, agitation, or respiratory depression may occur if absorbed systemically.
• Accidental intravascular injection: Must aspirate before and during administration to prevent systemic toxicity.
• Use with extreme caution in patients with hepatic impairment or severe renal disease.
• Resuscitation equipment and lipid emulsion therapy should be readily available in case of toxicity.

Common (Dose-dependent):

• Neurological: Dizziness, paresthesia, tremor
• Cardiovascular: Bradycardia, hypotension
• Gastrointestinal: Nausea, vomiting

Serious:

• CNS: Seizures, unconsciousness, coma
• Cardiac: Arrhythmias, cardiac arrest
• Allergic: Rash, urticaria, anaphylaxis (rare)
• Respiratory: Apnea, respiratory depression

• Other local anesthetics: Additive toxicity risk
• CNS depressants: Increased risk of sedation or respiratory depression
• Beta-blockers and calcium channel blockers: May exacerbate bradycardia or hypotension
• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): May reduce metabolism and increase toxicity
• Antiarrhythmic agents (e.g., amiodarone): May increase cardiac risk

• FDA and EMA emphasize avoidance of IV use due to severe cardiotoxicity.
• Lipid rescue therapy is now considered standard first-line treatment for bupivacaine-induced systemic toxicity.
• Guidelines now recommend ultrasound-guided nerve blocks to reduce accidental intravascular injection risk.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15–30°C.
• Protect from light and freezing.
• Single-dose vials should be used immediately after opening and discarded if not used.
• Do not use if solution is discolored or contains particles.
• Multidose vials should be used within the specified period once opened (e.g., 28 days unless specified).