What is the longest-acting local anesthetic?

Longest-Acting Local Anesthetics

Bupivacaine, levobupivacaine, and ropivacaine are the longest-acting local anesthetics available, with bupivacaine and levobupivacaine providing anesthesia lasting up to 7 hours in dental applications and significantly longer than intermediate-acting agents like lidocaine and mepivacaine across all regional anesthesia techniques. 1, 2

Duration Comparison

The long-acting local anesthetics are classified as a distinct pharmacologic category separate from short-acting (procaine, chloroprocaine) and intermediate-acting agents (lidocaine, mepivacaine, prilocaine). 3

Bupivacaine provides the longest duration among commonly used agents:

• Duration is 2-3 times longer than lidocaine and mepivacaine in dental procedures 2
• Can provide anesthesia lasting up to 7 hours in many patients 2
• Followed by a period of analgesia after sensation returns, reducing need for strong analgesics 2
• Peak plasma levels occur at 30-45 minutes, with decline to insignificant levels over 3-6 hours 2

Levobupivacaine offers equivalent duration to bupivacaine:

• Clinically equivalent in anesthetic potency and duration to bupivacaine 4
• Produces similar onset, duration, and density of block as bupivacaine at comparable doses 4
• Provides improved cardiovascular safety profile compared to racemic bupivacaine 4

Ropivacaine provides comparable long-acting anesthesia:

• Classified alongside bupivacaine and levobupivacaine as a long-acting agent in current guidelines 1, 5
• Allows higher maximum dosing (3 mg/kg vs 2.5 mg/kg for bupivacaine) 1, 5
• Offers potential advantages in cardiovascular safety over bupivacaine 6

Clinical Application Across Techniques

All three long-acting agents are recommended equivalently across regional anesthesia techniques by the European Society for Paediatric Anaesthesiology 2024 guidelines:

• Wound infiltration and peripheral nerve blocks 1
• Epidural blocks (thoracic and lumbar) 1
• Caudal blocks 1
• Paravertebral blocks 1
• Fascia iliaca and femoral nerve blocks 1
• TAP and rectus sheath blocks 1

Duration Enhancement Strategies

Adding epinephrine 1:200,000 prolongs duration:

• Reduces rate of absorption and peak plasma concentration 2
• Permits use of moderately larger total doses 2
• Sometimes prolongs duration of action 2

Adding preservative-free clonidine 1-2 mcg/kg extends block duration:

• Recommended across multiple block types in current guidelines 1, 5
• Provides reliable and predictable analgesia lasting 4-8 hours or longer 7
• Carries hemodynamic risks including hypotension and bradycardia requiring monitoring 8

Critical Safety Distinction

While all three agents provide equivalent duration, bupivacaine carries the highest cardiotoxicity risk, particularly after unintended intravascular injection, with potential for fatal ventricular arrhythmias and cardiac arrest. 2, 4 Levobupivacaine demonstrates significantly less CNS and cardiotoxicity than bupivacaine in preclinical and clinical studies, with less effect on myocardial contractility and QTc prolongation. 4