维基百科：局部麻醉(国外)

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A local anesthetic (LA) is a drug that causes reversible local anesthesia, generally for the aim of having a local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well. Also, when it is used on specific nerve pathways (nerve block), paralysis (loss of muscle power) can be achieved as well.

Clinical local anesthetics belong to one of two classes: aminoamide and aminoester local anesthetics. Synthetic local anesthetics are structurally related to cocaine. They differ from cocaine mainly in that they have no abuse potential and do not act on the sympathoadrenergic system, i.e. they do not produce hypertension or local vasoconstriction, with the exception of Ropivacaine and Mepivacaine that do produce weak vasoconstriction.

Mechanism of actionAll local anesthetics 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 local anesthetics (propranolol, for example). Local anesthetic 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 neurons that are rapidly firing. This is referred to as state dependent blockade.

Local anesthetics 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 local anesthetic binding site on the inside of the ion channel near the cytoplasmic end.

Acidosis such as caused by inflammation at a wound partly reduces the action of local anesthetics. 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 local anesthetics, but Agamma and Adelta fibres are most sensitive followed by Aalpha and beta fibres followed by type B and type C fibres in sensitivity,against previous view of sensitivity based on small fibre diameter and myelination . Thus, a differential block can be achieved (i.e. pain sensation is blocked more readily than other sensory modalities).

[edit] Specific uses[edit] Acute painAcute pain may occur due to trauma, surgery, infection, disruption of blood circulation or many other conditions in which there is tissue injury. In a medical setting it is usually desirable to alleviate pain when its warning function is no longer needed. Besides improving patient comfort, pain therapy can also reduce harmful physiological consequences of untreated pain.

Acute pain can often be managed using analgesics. However, conduction anesthesia may be preferable because of superior pain control and fewer side effects. For purposes of pain therapy, local anesthetic drugs are often given by repeated injection or continuous infusion through a catheter. Low doses of local anesthetic drugs can be sufficient so that muscle weakness does not occur and patients may be mobilized.

Some typical uses of conduction anesthesia for acute pain are:

Labor pain (epidural anesthesia)
Postoperative pain (peripheral nerve blocks, epidural anesthesia)
Trauma (peripheral nerve blocks, intravenous regional anesthesia, epidural anesthesia)
[edit] Chronic painChronic pain of more than minor intensity is a complex and often serious condition that requires diagnosis and treatment by an expert in pain medicine. Local anesthetics can be applied repeatedly or continuously for prolonged periods to relieve chronic pain, usually in combination with medication such as opioids, NSAIDs, and anticonvulsants.

Surgery, Podiatry and dentistryVirtually every part of the body can be anesthetized using conduction anesthesia. However, only a limited number of techniques are in common clinical use. Sometimes conduction anesthesia is combined with general anesthesia or sedation for the patient's comfort and ease of surgery. Typical operations performed under conduction anesthesia include:

Dentistry (surface anesthesia, infiltration anesthesia or intraligamentary anesthesia during restorative operations or extractions, regional nerve blocks during extractions and surgeries.)
Podiatry (Cutaneous, nail avulsions, matricectomy and various other podiatric procedures)
Eye surgery (surface anesthesia with topical anesthetics, retrobulbar block)
ENT operations, head and neck surgery (infiltration anesthesia, field blocks, peripheral nerve blocks, plexus anesthesia)
Shoulder and arm surgery (plexus anesthesia, intravenous regional anesthesia)[1]
Heart and lung surgery (epidural anesthesia combined with general anesthesia)
Abdominal surgery (epidural/spinal anesthesia, often combined with general anesthesia)
Gynecological, obstetrical and urological operations (spinal/epidural anesthesia)
Bone and joint surgery of the pelvis, hip and leg (spinal/epidural anesthesia, peripheral nerve blocks, intravenous regional anesthesia)
Surgery of skin and peripheral blood vessels (topical anesthesia, field blocks, peripheral nerve blocks, spinal/epidural anesthesia)
[edit] Other usesTopical anesthesia, in the form of lidocaine/prilocaine (EMLA) is most commonly used to enable relatively painless venipuncture (blood collection) and placement of intravenous cannulae. It may also be suitable for other kinds of punctures such as ascites drainage and amniocentesis.

Surface anesthesia also facilitates some endoscopic procedures such as bronchoscopy (visualization of the lower airways) or cystoscopy (visualization of the inner surface of the bladder).

TechniquesLocal anesthetics can block almost every nerve between the peripheral nerve endings and the central nervous system. The most peripheral technique is topical anesthesia to the skin or other body surface. Small and large peripheral nerves can be anesthetized individually (peripheral nerve block) or in anatomic nerve bundles (plexus anesthesia). Spinal anesthesia and epidural anesthesia merges into the central nervous system.

Injection of local anesthetics is often painful. A number of methods can be used to decrease this pain including buffering of the solution with bicarb and warming.[2]

Clinical techniques include:

Surface anesthesia - application of local anesthetic spray, solution or cream to the skin or a mucous membrane. The effect is short lasting and is limited to the area of contact.
Infiltration anesthesia - injection of local anesthetic into the tissue to be anesthetized. Surface and infiltration anesthesia are collectively topical anesthesia.
Field block - subcutaneous injection of a local anesthetic in an area bordering on the field to be anesthetized.
Peripheral nerve block - injection of local anesthetic in the vicinity of a peripheral nerve to anesthetize that nerve's area of innervation.
Plexus anesthesia - injection of local anesthetic in the vicinity of a nerve plexus, often inside a tissue compartment that limits the diffusion of the drug away from the intended site of action. The anesthetic effect extends to the innervation areas of several or all nerves stemming from the plexus.
Epidural anesthesia - a local anesthetic is injected into the epidural space where it acts primarily on the spinal nerve roots. Depending on the site of injection and the volume injected, the anesthetized area varies from limited areas of the abdomen or chest to large regions of the body.
Spinal anesthesia - a local anesthetic is injected into the cerebrospinal fluid, usually at the lumbar spine (in the lower back), where it acts on spinal nerve roots and part of the spinal cord. The resulting anesthesia usually extends from the legs to the abdomen or chest.
Intravenous regional anesthesia (Bier's block) - blood circulation of a limb is interrupted using a tourniquet (a device similar to a blood pressure cuff), then a large volume of local anesthetic is injected into a peripheral vein. The drug fills the limb's venous system and diffuses into tissues where peripheral nerves and nerve endings are anesthetized. The anesthetic effect is limited to the area that is excluded from blood circulation and resolves quickly once circulation is restored.
Local anesthesia of body cavities (e.g. intrapleural anesthesia, intraarticular anesthesia)

Transincision (or Transwound) catheter anesthesia, wherein a multilumen catheter is inserted through an insicion or wound and aligned across it on the inside as the incision or wound is closed, providing continuous administration of local anesthetic along the incision or wound.[3]
Undesired effects[edit] Localized adverse effectsThe local adverse effects of anesthetic agents include neurovascular manifestations such as prolonged anesthesia (numbness) and paresthesia (tingling, feeling of "pins and needles", or strange sensations). These are symptoms of localized nerve impairment or nerve damage.

RisksThe risk of temporary or permanent nerve damage varies between different locations and types of nerve blocks.[4]

RecoveryPermanent nerve damage after a peripheral nerve block is rare. Symptoms are very likely to resolve within a few weeks. The vast majority of those affected (92%–97%), recover within four to six weeks. 99% of these people have recovered within a year. It is estimated that between 1 in 5,000 and 1 in 30,000 nerve blocks result in some degree of permanent persistent nerve damage.[4]

It is suggested that symptoms may continue to improve for up to 18 months following injury.

CausesCauses of localized symptoms include:

neurotoxicity due to allergenic reaction,
excessive fluid pressure in a confined space,
severing of nerve fibers or support tissue with the needle/catheter,
injection-site hematoma that puts pressure on the nerve, or
injection-site infection that produces inflammatory pressure on the nerve and/or necrosis.
[edit] General adverse effects(See also local anesthetic toxicity)

General systemic adverse effects are due to the pharmacological effects of the anesthetic agents used. The conduction of electric impulses follows a similar mechanism in peripheral nerves, the central nervous system, and the heart. The effects of local anesthetics are therefore not specific for the signal conduction in peripheral nerves. Side effects on the central nervous system and the heart may be severe and potentially fatal. However, toxicity usually occurs only at plasma levels which are rarely reached if proper anesthetic techniques are adhered to. Additionally, persons may exhibit allergenic reactions to the anesthetic compounds and may also exhibit cyanosis due to methemoglobinemia.

Central nervous systemDepending on local tissue concentrations of local anesthetics, there may be excitatory or depressant effects on the central nervous system. At lower concentrations, a relatively selective depression of inhibitory neurons results in cerebral excitation, which may lead to generalized convulsions. A profound depression of brain functions occurs at higher concentrations which may lead to coma, respiratory arrest and death. Such tissue concentrations may be due to very high plasma levels after intravenous injection of a large dose. Another possibility is direct exposure of the central nervous system through the CSF, i.e., overdose in spinal anesthesia or accidental injection into the subarachnoid space in epidural anesthesia.

Cardiovascular systemThe conductive system of the heart is quite sensitive to the action of local anesthetic

Treatment of overdose: "Lipid rescue"There is evidence that Intralipid, a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anesthetic overdose, including human case reports of successful use in this way ('lipid rescue').[5][6][7][8][9]

Hypersensitivity/allergyAdverse reactions to local anesthetics (especially the esters) are not uncommon, but true allergy is very rare. Allergic reactions to the esters is usually due to a sensitivity to their metabolite, para-aminobenzoic acid (PABA), and does not result in cross-allergy to amides. Therefore, amides can be used as alternatives in those patients. Non-allergic reactions may resemble allergy in their manifestations. In some cases, skin tests and provocative challenge may be necessary to establish a diagnosis of allergy. There are also cases of allergy to paraben derivatives, which are often added as preservatives to local anesthetic solutions.

Stub: Allergic reactions during anesthesia
MethemoglobinemiaThe systemic toxicity of prilocaine is comparatively low, however its metabolite, o-toluidine, is known to cause methemoglobinemia. As methemoglobinemia reduces the amount of hemoglobin that is available for oxygen transport, this side effect is potentially life-threatening. Therefore dose limits for prilocaine should be strictly observed. Prilocaine is not recommended for use in labor pains or infants.

Local anesthetics in clinical useEsters are prone to producing allergic reactions, which may necessitate the use of an Amide. The names of each locally clinical anesthetic have the suffix "-caine". In general Amides have two "i"'s in their nomenclature while the Esters only have one.

Most ester local anesthetics are metabolized by pseudocholinesterases, while amide local anesthetics are metabolized in the liver. This can be a factor in choosing an agent in patients with liver failure.[10]

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