A local anesthetic (LA) is a medication that causes reversible absence of pain sensation, although other senses are often affected, as well. Also, when it is used on specific nerve pathways (local anesthetic nerve block), paralysis (loss of muscle power) also can be achieved. Clinical LAs belong to one of two classes: aminoamide and aminoester local anesthetics. Synthetic LAs are structurally related to cocaine. They differ from cocaine mainly in that they have a very low abuse potential and do not produce hypertension or (with few exceptions) vasoconstrictions.
Types of Anesthesia
There are three main categories of anesthesia, each having many forms and uses. They are
Regional anesthesia is used to numb only the portion of the body that will undergo the surgery. Usually, an injection of local anesthetic is given in the area of nerves that provide feeling to that part of the body. There are several forms of regional anesthetics:
- Spinal anesthetic –A spinal anesthetic is used for lower abdominal, pelvic, rectal, or lower extremity surgery. This type of anesthetic involves injecting a single dose of anesthetic medicine into the area that surrounds the spinal cord. The injection is made into the lower back, below the end of the spinal cord, and causes numbness in the lower body. This type of anesthesia is most often used in orthopedic procedures of the lower extremities.
- Epidural anesthetic – The epidural anesthetic is similar to a spinal anesthetic and is commonly used for surgery of the lower limbs and during labor and childbirth. This type of anesthesia involves continually infusing an anesthetic medicine through a thin catheter (hollow tube). The catheter is placed into the space that surrounds the spinal cord in the lower back, causing numbness in the lower body. Epidural anesthesia may also be used for chest or abdominal surgery. In this case, the anesthetic medicine is injected at a higher location in the back to numb the chest and abdominal areas.
According to Procedure or function
Topical – Applied to the mucous membrane.
Infiltration – Injected into tissues.
Field block – Injected into subcutaneous layer.
Nerve block – Injected into the peripheral nerve.
Spinal – Injected into CSF of the lumbar region.
Intravenous – Injected into nerve trunks and endings.
Epidural – Injected into epidural space.
According to the Source
Synthetic nitrogenous agent
- p-aminobenzoic acid derivatives– Procaine, Benzocaine, Butamben, Butacaine
- Anilides– Mepivacaine, Lidocaine, Bupivacaine
- Quinoline derivatives– Cinchocaine, Dimethylisoquine
Synthetic non-nitrogenous agent
- Benzoyl alcohol, Propandiol
Local anesthetic solutions for injection typically consist of
- The local anesthetic agent itself
- A vehicle, which is usually water-based or just sterile water
- Vasoconstrictor possibly (see below)
- Reducing agent (antioxidant), e.g. if epinephrine is used, then sodium metabisulfite is used as a reducing agent
- Preservative, e.g. methylparaben
Sometimes, local anesthesia are combined, with
- Lidocaine/prilocaine (EMLA, eutectic mixture of local anesthetic)
- Lidocaine/tetracaine (Rapydan)
- Prilocaine hydrochloride and epinephrine (trade name Citanest Forte)
- Lidocaine, bupivacaine, and epinephrine (recommended final concentrations of 0.5, 0.25, and 0.5%, respectively)
- Iontocaine, consisting of lidocaine and epinephrine
- Septocaine (trade name Septodont), a combination of articaine and epinephrine
One combination product of this type is used topically for surface anaesthesia, TAC (5-12% tetracaine,1/2000 (0.05%, 500 ppm, ½ per mille) adrenaline, 4 or 10% cocaine).
Naturally occurring local anesthetics not derived from cocaine are usually neurotoxins, and have the suffix -toxin in their names. Unlike cocaine produced local anesthetics which are intracellular in effect, saxitoxin, neosaxitoxin & tetrodotoxin bind to the extracellular side of sodium channels.
Mechanism of action of Anesthesia
All LAs are membrane-stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like nociceptors). Though many other drugs also have membrane-stabilizing properties, not all are used as LAs (propranolol, for example). LA drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the so-called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Local anesthetic drugs bind more readily to sodium channels in an activated state, thus onset of neuronal blockade is faster in rapidly firing neurons. This is referred to as state-dependent blockade.
LAs are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. At a pH equal to the protonated base’s pKa, the protonated (ionized) and unprotonated (unionized) forms of the molecule exist in equimolar amounts, but only the unprotonated base diffuses readily across cell membranes. Once inside the cell, the local anesthetic will be in equilibrium, with the formation of the protonated (ionized) form, which does not readily pass back out of the cell. This is referred to as “ion-trapping”. In the protonated form, the molecule binds to the LA binding site on the inside of the ion channel near the cytoplasmic end. Most LAs work on the internal surface of the membrane – the drug has to penetrate the cell membrane, which is achieved best in the nonionised form.
Acidosis such as caused by inflammation at a wound partly reduces the action of LAs. This is partly because most of the anesthetic is ionized and therefore unable to cross the cell membrane to reach its cytoplasmic-facing site of action on the sodium channel.
All nerve fibers are sensitive to LAs, but due to a combination of diameter and myelination, fibers have different sensitivities to LA blockade, termed differential blockade. Type B fibers (sympathetic tone) are the most sensitive followed by type C (pain), type A delta (temperature), type A gamma (proprioception), type A beta (sensory touch and pressure), and type A alpha (motor). Although type B fibers are thicker than type C fibers, they are myelinated, thus are blocked before the unmyelinated, thin C fiber.
Medical Uses of Anesthesia
The purpose of anesthesia can be distilled down to three basic goals or end points
- hypnosis (a temporary loss of consciousness and with it a loss of memory. In a pharmacological context, the word hypnosis usually has this technical meaning, in contrast to its more familiar lay or psychological meaning of an altered state of consciousness not necessarily caused by drugs—see hypnosis).
- analgesia (lack of sensation which also blunts autonomic reflexes)
- muscle relaxation
Different types of anesthesia (which are discussed in the following sections) affect the endpoints differently. Regional anesthesia, for instance, affects analgesia; benzodiazepine-type sedatives (used in twilight sleep) favor amnesia; and general anesthetics can affect all of the endpoints. The goal of anesthesia is to achieve the endpoints required for the given surgical procedure with the least risk to the patient.
To achieve the goals of anesthesia, drugs act on different but interconnected parts of the nervous system. Hypnosis, for instance, is generated through actions on the nuclei in the brain and is similar to the activation of sleep. The effect is to make people less aware and less reactive to noxious stimuli.
Loss of memory (amnesia) is created by action of drugs on multiple (but specific) regions of the brain. Memories are created as either declarative or non-declarative memories in several stages (short-term, long-term, long-lasting) the strength of which is determined by the strength of connections between neurons termed synaptic plasticity. Each anesthetic produces amnesia through unique effects on memory formation at variable doses. Inhalational anesthetics will reliably produce amnesia through general suppression of the nuclei at doses below those required for loss of consciousness. Drugs like midazolam produce amnesia through different pathways by blocking the formation of long-term memories.
When pain is blocked from a part of the body using local anesthetics, it is generally referred to as regional anesthesia. There are many types of regional anesthesia either by injecting into the tissue itself, a vein that feeds the area or around a nerve trunk that supplies sensation to the area. The latter are called nerve blocks and are divided into peripheral or central nerve blocks.
The following are the types of regional anesthesia
- Infiltrative anesthesia – a small amount of local anesthetic is injected in a small area to stop any sensation (such as during the closure of a laceration, as a continuous infusion or “freezing” a tooth). The effect is almost immediate.
- Peripheral nerve block – local anesthetic is injected near a nerve that provides sensation to particular portion of the body. There is significant variation in the speed of onset and duration of anesthesia depending on the potency of the drug
- Intravenous regional anesthesia (also called a Bier block) – dilute local anesthetic is infused to a limb through a vein with a tourniquet placed to prevent the drug from diffusing out of the limb.
- Central nerve blockade – Local anesthetic is injected or infused in or around a portion of the central nervous system (discussed in more detail below in Spinal, epidural and caudal anesthesia).
- Topical anesthesia – local anesthetics that are specially formulated to diffuse through the mucous membranes or skin to give a thin layer of analgesia to an area (e.g. EMLA patches).
- Tumescent anesthesia – a large amount of very dilute local anesthetics are injected into the subcutaneous tissues during liposuction.
- Systemic local anesthetics – local anesthetics are given systemically (orally or intravenous) to relieve neuropathic pain
When local anesthetic is injected around a larger diameter nerve that transmits sensation from an entire region it is referred to as a nerve block or regional nerve blockade. Nerve blocks are commonly used in dentistry, when the mandibular nerve is blocked for procedures on the lower teeth. With larger diameter nerves (such as the interscalene block for upper limbs or psoas compartment block for lower limbs) the nerve and position of the needle is localized with ultrasound or electrical stimulation. The use of ultrasound may reduce complication rates and improve quality, performance time, and time to onset of blocks. Because of the large amount of local anesthetic required to affect the nerve, the maximum dose of local anesethetic has to be considered. Nerve blocks are also used as a continuous infusion, following major surgery such as knee, hip and shoulder replacement surgery, and may be associated with lower complications.Nerve blocks are also associated with a lower risk of neurologic complications compared to the more central epidural or spinal neuraxial blocks.
Spinal, epidural and caudal anesthesia
Central neuraxial anesthesia is the injection of local anesthetic around the spinal cord to provide analgesia in the abdomen, pelvis or lower extremities. It is divided into either spinal (injection into the subarachnoid space), epidural (injection outside of the subarachnoid space into the epidural space) and caudal (injection into the cauda equina or tail end of the spinal cord). Spinal and epidural are the most commonly used forms of central neuraxial blockade.
Spinal anesthesia – is a “one-shot” injection that provides rapid onset and profound sensory anesthesia with lower doses of anesethetic, and is usually associated with neuromuscular blockade (loss of muscle control). Epidural anesthesia uses larger doses of anesthetic infused through an indwelling catheter which allows the anesthetic to be augmented should the effects begin to dissipate. Epidural anesthesia does not typically affect muscle control.
Because central neuraxial blockade causes arterial and vasodilation, a drop in blood pressure is common. This drop is largely dictated by the venous side of the circulatory system which holds 75% of the circulating blood volume. The physiologic effects are much greater when the block is placed above the 5th thoracic vertebra. An ineffective block is most often due to inadequate anxiolysis or sedation rather than a failure of the block itself
Acute pain management
Pain that is well managed during and immediately after surgery improves the health of patients (by decreasing physiologic stress) and the potential for chronic pain. Nociception (pain sensation) is not hard-wired into the body. Instead, it is a dynamic process wherein persistent painful stimuli can sensitize the system and either make pain management difficult or promote the development of chronic pain. For this reason, preemptive acute pain management may reduce both acute and chronic pain and is tailored to the surgery, the environment in which it is given (in-patient/out-patient) and the individual patient.