Medical Pharmacology Chapter 15: Local Anesthesics

Vasocontrictors added to local anesthetic solutions

• Purpose of adding epinephrine to a local anesthetic solution: Increased duration: addition of epinephrine (1:2000,000 or 5 μg/ml) to cause vasoconstriction

  • Reduced systemic absorption

  • Higher anesthetic concentration near nerve fibers

  • Prolongation of conduction blockade (about 50% longer)

  • Reduced systemic absorption (by about 33%)

• Factors influencing the effectiveness of epinephrine on local anesthesia:

  • Which anesthetic is used:

    •  Reduced effect of epinephrine on duration of conduction blockade and systemic absorption comparing mepivacaine (Carbocaine) and etidocaine (Duranest) [these are more lipophilic]  with lidocaine (Xylocaine), which is less lipophilic

      •  More lipophilic local anesthetics will tend on their own to associate strongly with tissues

  • Level of sensory blockade needed for spinal or epidural anesthesia

    • Duration of lower extremity sensory anesthesia extended by epinephrine or phenylephrine (Neo-Synephrine); this effect is not observed for abdominal region anesthesia

      • Conditions: epinephrine (0.2 mg) or phenylephrine (Neo-Synephrine) (2 mg) added to mepivacaine (Carbocaine) or lidocaine (Xylocaine) -- placed in subarachnoid spaces

  • Spinal anesthesia e.g. tetracaine (pontocaine).  The duration of action is extended by vasoconstrictors

    • Condition 1: epinephrine plus tetracaine (pontocaine) (6 mg, low-dose)- result: increase in spinal anesthesia success rate

    • Condition 2: epinephrine plus tetracaine (pontocaine) (10 mg, higher dose)- result: no increase in spinal anesthesia success rate

• Mechanism of vasoconstrictor mediated prolongation of local anesthetic action (no effect by epinephrine on time-to-onset):

  • Decreased systemic absorption

  • Increased local anesthetic concentration in the vicinity of sensory nerves

  • Increased uptake of the local anesthetic

• Advantages of reduced local anesthetic systemic absorption:

  • Local anesthetic absorption rate more likely to match metabolic rate resulting in less local anesthetic systemic toxicity.

•  Toxicities associated with systemic epinephrine absorption:

  • Local anesthetic + epinephrine:­ increased cardiac irritability which may cause an increased risk of cardiac arrhythmias.

  • Increased possibility of hypertensive response in susceptible patients.

• Other agents which may be added to local anesthetics that affect duration of action.

  • Dextran (low-molecular-weight) when added to local anesthetic solutions result in increased peripheral nerve block anesthesia duration, probably due to a reduction in local anesthetic systemic absorption.