Bupivacaine

Bupivacaine is a long-acting amide-type local anesthetic commonly used in various forms of regional anesthesia. It functions by inhibiting sodium channels on nerve membranes, thereby preventing the initiation and conduction of nerve impulses. Bupivacaine's high potency and prolonged duration of action make it a preferred agent for surgical, obstetric, and postoperative pain management.

Uses:

1. Regional Anesthesia: Epidural, spinal, and peripheral nerve blocks for surgical procedures.
2. Postoperative Pain Management: Continuous infusion or single-injection techniques.
3. Labor Analgesia: Epidural anesthesia for pain relief during childbirth.
4. Chronic Pain Management: Nerve blocks for patients with chronic pain conditions.

Dosage and Administration:

Adults:

• Epidural Anesthesia: Initial dose: 10-20 mL of 0.25% to 0.5% solution.
• Continuous Epidural: 6-10 mL of 0.125% to 0.25% solution per hour.
• Spinal Anesthesia: 0.5% solution, 1.5-3 mL for a block lasting 2-4 hours.

Pediatrics:

• Caudal or Epidural Block: 0.25-0.5 mg/kg, adjusted based on weight and clinical response.
• Subarachnoid Block (Infants):
  • <5 kg: 1 mg/kg
  • 5-15 kg: 0.4 mg/kg
  • 15 kg: 0.3 mg/kg

Toxic Dose:

• Without epinephrine: 2.5 mg/kg (total dose < 175 mg per single injection).
• With epinephrine: 3 mg/kg (total dose < 225 mg).

Dose Adjustment in Different Diseases:

• Hepatic Impairment: Use with caution; consider reducing the dose due to impaired metabolism.
• Renal Impairment: Minimal adjustment required, but monitor for accumulation with prolonged use.
• Cardiovascular Disease: Lower doses recommended to reduce the risk of cardiotoxicity.

Drug Combinations in Use:

• Epinephrine: Prolongs duration and decreases systemic absorption.
• Opioids (e.g., fentanyl): Enhance analgesic effects during epidural analgesia.
• Clonidine: Potentiates nerve block duration.
• NSAIDs: Used adjunctively for postoperative pain relief.

Presentation/Form:

• Injection Solutions: Available in 0.25%, 0.5%, and 0.75% concentrations.
• Spinal Anesthesia (Bupivacaine Heavy): 0.5% heavy solution containing 8% glucose.
• Isobaric Formulation: 0.5% plain solution with density similar to cerebrospinal fluid.
• Liposomal Bupivacaine (EXPAREL): Long-acting formulation for postsurgical analgesia.

Pharmacokinetics:

• Absorption: Dependent on site of administration and vascularity.
• Distribution: Highly protein-bound (95%).
• Metabolism: Primarily metabolized in the liver by cytochrome P450 enzymes.
• Elimination Half-life: Approximately 3.5 hours in adults.
• Excretion: Metabolites primarily excreted via urine.

Pharmacodynamics:

• Onset: 10-20 minutes depending on the route.
• Duration: 6-8 hours for peripheral nerve blocks; up to 72 hours with liposomal formulation.
• Selective sensory block at low concentrations.

Drug Interactions:

• Beta-blockers and Antiarrhythmics (e.g., amiodarone): Increase cardiodepressive effects.
• Epinephrine: Enhances duration and reduces systemic absorption.
• MAO Inhibitors and Tricyclic Antidepressants: Potentiate the effects of bupivacaine.
• Drugs Prolonging QT Interval: Caution advised.

Comparison with Other Drugs in the Same Category:

Parameter	Bupivacaine	Ropivacaine	Levobupivacaine
Potency	High	Moderate	High
Cardiotoxicity	Higher	Lower	Lower
Onset	10-20 minutes	10-15 minutes	10-15 minutes
Duration	6-8 hours	4-6 hours	6-8 hours
Sensory vs. Motor Block	More sensory selective	Similar	Similar

Precautions and Special Considerations:

• Pregnancy: Category C; use with caution.
• Elderly: Increased sensitivity; consider dose reduction.
• Liver Dysfunction: Monitor closely due to reduced metabolism.
• Allergic Reactions: Rare but possible.
• IV Regional Anesthesia: Contraindicated due to cardiotoxicity risk.

Side Effects:

• Common: Hypotension, bradycardia, nausea, vomiting, shivering.
• Serious: Local Anesthetic Systemic Toxicity (LAST), CNS symptoms (tinnitus, confusion, seizures), cardiovascular collapse (arrhythmias, cardiac arrest).

Local Anesthetic Systemic Toxicity (LAST):

• Signs: Dizziness, circumoral numbness, tinnitus, CNS depression.
• Management:
  • Stop bupivacaine immediately.
  • Airway support.
  • Administer 20% lipid emulsion therapy (1.5 mL/kg bolus, followed by 0.25 mL/kg/min infusion).
  • Follow ACLS protocols for cardiovascular collapse.

Recent Updates and Guidelines:

• Liposomal bupivacaine (EXPAREL) has gained traction for enhanced postoperative analgesia.
• Updated guidelines emphasize cautious dosing to reduce LAST risk.
• Advances in drug delivery methods (e.g., catheters for continuous infusion).

Facts to Remember:

• Bupivacaine has a higher risk of cardiotoxicity compared to other local anesthetics.
• Differential nerve block properties provide sensory blockade at low concentrations.
• Liposomal formulations extend analgesia up to 72 hours.
• Monitoring for LAST is essential during high-dose or prolonged administration.

References:

1. NCBI StatPearls - Bupivacaine: Link
2. PMC - Bupivacaine Review: Link
3. Stoelting’s Pharmacology and Physiology in Anesthetic Practice, 5th edition