Local Anesthetics

Local anesthetics (LA) are used widely throughout medicine. Their purpose is to blunt the pain typically associated with some type of procedure. They are also one of the oldest known medications, dating back to the time of the Incas. We use a wide variety of different types and concentrations of LAs depending on their purpose. In Anesthesiology, we commonly use bupivacaine for regional blocks, epidurals, and spinals. We also use lidocaine subcutaneously when placing lines such as a central venous catheter.

The mechanism of action of LAs is to block voltage-gated Na channels on nerve fibers. Trauma will create a local reaction of inflammatory cytokines that activate nociceptors  found on nerve endings. This then activates Na channels involved in initiating and propagating action potentials in axons, dendrites, and muscle tissue. By blocking the influx of Na into the cell, you restrict the cell’s ability to depolarize, ultimately disrupting transmission of the nerve’s signal. The non-ionized form of the LA travels through the cellular membrane to bind the a-subunit of the Na channel intracellularly. Sodium channels are also found on myocardium cells. Lidocaine and bupivacaine both will block sodium channels in the heart. This can both be beneficial (lidocaine for ventricular tachycardias) and detrimental (heart block with high doses of bupivacaine).

LAs are usually described by their speed of onset, duration of action, and potency. These characteristics help determine which LA is best for a particular scenario.

Speed of onset is determined by pKa. As the pKa decreases and gets closer to physiologic pH (7.40), there are more non-ionized LA molecules that can cross into the intracellular space. Lidocaine has a pKa of 7.7 and has a much faster onset compare to Bupivacaine which has a pKa of 8.1. Inflammation and infection can cause tissue to become acidodic, creating more ionized molecules of LA and make them less effective. Bicarbonate will increase the onset of action since it will increase the pH of the local tissue as it gets injected.

Potency is related to lipid solubility. The greater the lipid solubility, the quicker the LA can rapidly diffuse through the lipid bilayer to reach its site of action. Because of this, lipid solubility also plays a role in onset of action. The addition of opiates to LA in neuraxial blocks will create a more potent or “denser” blockade.

Duration of action is determined by the percentage of LA bound to protein. The higher the protein binding percentage of a LA, the longer the duration of action. Hypoxia, hypercarbia, and acidemia will all decrease protein binding and increase the risk of local anesthetic toxicity. Epinephrine can be added to LA to increase the duration of action by causing vasoconstriction and decreasing uptake into the bloodstream.