View source for Local anesthetic

{{Short description|Medications to reversibly block pain}}
{{For|the novel by Günter Grass|Local Anaesthetic (novel)}}
{{Use dmy dates|date=April 2023}}
[[File:Local anesthetics general structure.svg|class=skin-invert-image|thumb|Many local anesthetics fall into two general chemical classes, amino esters (top) and amino amides (bottom).]]

A '''local anesthetic''' ('''LA''') is a [[medication]] that causes absence of all [[sense|sensation]] (including [[pain]]) in a specific body part without loss of consciousness,<ref name="nhs.uk">{{Cite web |date=2017-10-17 |title=Types of Anaesthesia |url=https://www.nhs.uk/conditions/anaesthesia/ |access-date=2023-04-10 |website=nhs.uk}}</ref> providing [[local anesthesia]], as opposed to a [[general anesthetic]], which eliminates all sensation in the entire body and causes [[unconsciousness]].<ref name="nhs.uk" /> Local anesthetics are most commonly used to eliminate pain during or after surgery.<ref>{{Cite web |date=2017-10-19 |title=Local anaesthesia |url=https://www.nhs.uk/conditions/local-anaesthesia/#:~:text=Local%20anaesthesia%20involves%20numbing%20an,or%20relieve%20pain%20after%20surgery. |access-date=2023-04-10 |website=nhs.uk}}</ref> When it is used on specific nerve pathways ([[local anesthetic nerve block]]), [[paralysis]] (loss of muscle function) also can be induced.<ref>{{Cite journal |last1=Greenbaum |first1=R. A. |last2=Kaye |first2=G. |last3=Mason |first3=P. D. |date=July 1987 |title=Experience with nalbuphine, a new opioid analgesic, in acute myocardial infarction |journal=Journal of the Royal Society of Medicine |volume=80 |issue=7 |pages=418–421 |doi=10.1177/014107688708000708 |issn=0141-0768 |pmc=1290901 |pmid=3309298}}</ref>

==Classification==
LAs are of 2 types:
*Clinical LAs:
**[[amino amide]] LAs 
**[[amino ester]] LAs
*Synthetic LAs
**[[Cocaine]] derivatives

Synthetic cocaine-derived LAs differ from cocaine because they have a much lower [[abuse potential]] and do not cause [[hypertension]] [[vasoconstriction]] (with few exceptions).

The suffix "-caine" at the ends of these medication names is derived from the word "[[cocaine]]", because cocaine was formerly used as a local anesthetic.

== Examples ==
'''Short Duration of Action and Low Potency'''

*[[Benzocaine]]
*[[Procaine]]
*[[Chloroprocaine]]
*[[Cocaine]]

'''Medium Duration of Action and Medium Potency'''

*[[Lidocaine]]
*[[Prilocaine]]

'''High Duration and High Potency'''

*[[Tetracaine]]
*[[Bupivacaine]]
*[[Cinchocaine]]
*[[Ropivacaine]]

== Medical uses ==
Local anesthetics may be used to prevent and/or treat acute pain, to treat chronic pain, and as a supplement to general anesthesia.

They are used in various techniques of [[local anesthesia]] such as:
* [[Topical anesthesia]] (surface anesthesia)
* Topical administration of cream, gel, ointment, liquid, or spray of anesthetic dissolved in [[DMSO]] or other solvents/carriers for deeper absorption
* [[Infiltration (medical)|Infiltration]]
* [[Brachial plexus block]]
* [[Epidural|Epidural block]] (extradural)
* [[Spinal anaesthesia|Spinal anesthesia]] (subarachnoid block)
* [[Iontophoresis]]
* Diagnostic purposes (e.g. [[dibucaine]])
*[[Anti-arrhythmic]] agents (e.g. lidocaine).<ref name="Heavner2017">{{cite book |last=Heavner |first=James E. |title=Local Anesthetics |date=2017 |url=http://accessanesthesiology.mhmedical.com/content.aspx?aid=1144119460 |work=Anesthesiology |editor-last=Longnecker |editor-first=David E. |access-date=2023-04-10 |edition=3 |place=New York, NY |publisher=McGraw-Hill Education |editor2-last=Mackey |editor2-first=Sean C. |editor3-last=Newman |editor3-first=Mark F. |editor4-last=Sandberg |editor4-first=Warren S.}}</ref>

===Acute pain===
Even though [[acute pain]] can be managed using [[analgesic]]s, conduction anesthesia may be preferable because of superior pain control and fewer side effects.{{citation needed|date=January 2023}} For purposes of pain therapy, LA drugs are often given by repeated injection or continuous infusion through a catheter. LA drugs are also often combined with other agents such as opioids for synergistic analgesic action.<ref>{{cite journal | vauthors = Ryan T, Hodge A, Holyoak R, Vlok R, Melhuish T, Binks M, Hurtado G, White L | display-authors = 6 | title = Tramadol as an adjunct to intra-articular local anesthetic infiltration in knee arthroscopy: a systematic review and meta-analysis | journal = ANZ Journal of Surgery | volume = 89 | issue = 7–8 | pages = 827–832 | date = July 2019 | pmid = 30684306 | doi = 10.1111/ans.14920 | s2cid = 59275648 }}</ref>  Low doses of LA drugs can be sufficient so that muscle weakness does not occur and patients may be mobilized.{{citation needed|date=February 2022}}

Some typical uses of conduction anesthesia for acute pain are:
{| {{table}}
! Type of pain 
! Possible treatments
|-
|[[Labor pain]]
|[[Epidural anesthesia]], [[Pudendal nerve block]]s
|-
|[[Postoperative pain]] 
|[[Peripheral nerve block]]s, epidural anesthesia
|-
|[[Injury|Trauma]]
|Peripheral nerve blocks, [[intravenous regional anesthesia]], epidural anesthesia
|}

===Chronic pain===

[[Chronic pain]] is a complex and often serious condition that requires diagnosis and treatment by an expert in pain medicine. LAs can be applied repeatedly or continuously for prolonged periods to relieve chronic pain, usually in combination with medication such as [[opioid]]s, [[NSAID]]s, and [[anticonvulsant]]s. Though it can be easily performed, repeated local anesthetic blocks in chronic pain conditions are not recommended as there is no evidence of long-term benefits.<ref>{{cite journal | vauthors =  | title = Current world literature. Drugs in anaesthesia | journal = Current Opinion in Anesthesiology | volume = 16 | issue = 4 | pages = 429–436 | date = August 2003 | pmid = 17021493 | doi = 10.1097/00001503-200308000-00010 }}</ref>

=== Surgery ===
Virtually 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. However, many anesthetists, surgeons, patients and nurses believe that it is safer to perform major surgeries under local anesthesia than general anesthesia.<ref name="pmid19918020">{{cite journal | vauthors = Bodenham AR, Howell SJ | title = General anaesthesia vs local anaesthesia: an ongoing story | journal = British Journal of Anaesthesia | volume = 103 | issue = 6 | pages = 785–789 | date = December 2009 | pmid = 19918020 | doi = 10.1093/bja/aep310 | doi-access = free }}</ref> Typical operations performed under conduction anesthesia include:
{| {{table}}
! Type of surgery
! Purposes or procedures
|-
|[[Dentistry]]
|[[topical anesthesia]] (surface anesthesia), [[infiltration anesthesia]] and [[intraligamentary anesthesia]] during restorative operations such as fillings, crowns, and root canals,<ref name="Torpy2011">{{cite journal | vauthors = Torpy JM, Lynm C, Golub RM | title = JAMA patient page. Local anesthesia | journal = JAMA | volume = 306 | issue = 12 | pages = 1395 | date = September 2011 | pmid = 21954483 | doi = 10.1001/jama.306.12.1395 | doi-access = free}}</ref> or extractions, and regional nerve blocks during extractions and surgeries
|-
|[[Podiatry]]<br>(surgery of feet, ankles, and legs)
|[[cutaneous anesthesia]], [[nail avulsion]]s, [[matricectomy]], [[bunionectomy]], [[hammertoe repair]]<ref name="Torpy2011" /> and various other podiatric procedures
|-
|[[Eye surgery]]
|surface anesthesia with [[topical anesthetic]]s or [[retrobulbar block]] during cataract removal or other ophthalmic procedures<ref name="Torpy2011" />
|-
|[[Head and neck surgery]]<br>(ENT operations)
|infiltration anesthesia, field blocks, or peripheral nerve blocks, [[plexus anesthesia]]
|-
|[[Shoulder surgery]]<br>[[Arm surgery]]
|plexus anesthesia or intravenous regional anesthesia<ref>{{cite journal | vauthors = Brown AR, Weiss R, Greenberg C, Flatow EL, Bigliani LU | title = Interscalene block for shoulder arthroscopy: comparison with general anesthesia | journal = Arthroscopy | volume = 9 | issue = 3 | pages = 295–300 | year = 1993 | pmid = 8323615 | doi = 10.1016/S0749-8063(05)80425-6 }}</ref>
|-
|[[Cardiac surgery]] (heart surgery)<br>[[Pulmonary surgery]] (lung surgery)
|epidural anesthesia combined with general anesthesia
|-
|[[Abdominal surgery]]
|epidural anesthesia or [[spinal anesthesia]], often combined with general anesthesia during inguinal hernia repair or other abdominal surgery<ref name="Torpy2011" />
|-
|[[Gynecological surgery]]<br>[[Obstetric surgery]]<br>[[Urological surgery]] 
|spinal anesthesia or epidural anesthesia
|-
|[[Bone surgery]] and [[joint surgery]] of the [[pelvis]], [[hip]], and [[leg]] 
|spinal anaesthesia or epidural anesthesia, peripheral nerve blocks, or intravenous regional anesthesia
|-
|[[Skin surgery]] and [[peripheral vascular surgery]]
|[[topical anesthesia]], [[field block]]s, peripheral nerve blocks, spinal anesthesia or epidural anesthesia<ref>{{Cite journal |last1=Flaherty |first1=James |last2=Horn |first2=Jean-Louis |last3=Derby |first3=Ryan |date=September 2014 |title=Regional anesthesia for vascular surgery |url=https://pubmed.ncbi.nlm.nih.gov/25113725/ |journal=Anesthesiology Clinics |volume=32 |issue=3 |pages=639–659 |doi=10.1016/j.anclin.2014.05.002 |issn=1932-2275 |pmid=25113725}}</ref>
|}

=== Diagnostic tests ===
Diagnostic tests such as bone marrow aspiration, lumbar puncture (spinal tap) and aspiration of cysts or other structures are made to be less painful upon administration of local anesthetic before insertion of larger needles.<ref name="Torpy2011" />

=== Other uses ===
Local anesthesia is also used during insertion of IV devices, such as pacemakers and implantable defibrillators, ports used for giving chemotherapy medications and hemodialysis access catheters.<ref name="Torpy2011" />

Topical anesthesia, in the form of [[lidocaine/prilocaine]] (EMLA) is most commonly used to enable relatively painless [[venipuncture]] ([[blood]] collection) and placement of [[Peripheral venous catheter|intravenous cannula]]e. It may also be suitable for other kinds of punctures such as [[ascites]] drainage and [[amniocentesis]].

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

== Side effects ==

===Localized side effects===
Edema of tongue, pharynx and larynx may develop as a side effect of local anesthesia. This could be caused by a variety of reasons including trauma during injection, infection, an allergic reaction, haematoma or injection of irritating solutions such as cold-sterilization solutions. Usually there is tissue swelling at the point of injection. This is due to puncturing of the vein which allows the blood to flow into loose tissues in the surrounding area. Blanching of the tissues in the area where the local anesthetic is deposited is also common. This gives the area a white appearance as the blood flow is prevented due to vasoconstriction of arteries in the area. The vasoconstriction stimulus gradually wears off and subsequently the tissue returns to normal in less than two hours.<ref name="P. 2016">{{Cite book|title=Manual of local anaesthesia in dentistry. | vauthors = Chitre AP |date=2016|publisher=Jaypee Brothers Medical P|isbn=978-9352501984|location=[Place of publication not identified] |oclc=930829770}}</ref>

The side effects of inferior alveolar nerve block include feeling tense, clenching of the fists and moaning.<ref name="worldcat.org">{{Cite book|title=Successful local anesthesia for restorative dentistry and endodontics| vauthors = Reader A, Nusstein J, Drum M |date=12 September 2014|isbn=9780867156157|location=Chicago|oclc=892911544}}</ref>

The duration of soft tissue anesthesia is longer than pulpal anesthesia and is often associated with difficulty eating, drinking and speaking.<ref name="worldcat.org"/>

====Risks====
The risk of temporary or permanent nerve damage varies between different locations and types of [[nerve block]]s.<ref name="RoyalCol">{{Cite journal|journal=Risks Associated with Your Anesthetic|title=Nerve damage associated with peripheral nerve block|volume=Section 12|date=January 2006|url=http://www.rcoa.ac.uk/docs/nerve-peripheral.pdf|access-date=2007-10-10|archive-url=https://web.archive.org/web/20071009110706/http://www.rcoa.ac.uk/docs/nerve-peripheral.pdf|archive-date=2007-10-09|url-status=dead}}</ref>

There is risk of accidental damage to local blood vessels during injection of the local anesthetic solution. This is referred to as [[Hematoma|haematoma]] and could result in pain, [[trismus]], swelling and/or discolouration of the region. The density of tissues surrounding the injured vessels is an important factor for haematoma. There is greatest chance of this occurring in a posterior superior alveolar nerve block or in a pterygomandibular block.{{citation needed|date=February 2022}}

Giving local anesthesia to patients with liver disease can have significant consequences. Thorough evaluation of the disease should be carried out to assess potential risk to the patient as in significant liver dysfunction, the half-life of amide local anesthetic agents may be drastically increased thus increasing the risk of overdose.

Local anesthetics and vasoconstrictors may be administered to pregnant patients however it is very important to be extra cautious when giving a pregnant patient any type of drug. Lidocaine can be safely used but bupivacaine and mepivacaine should be avoided.  Consultation with the obstetrician is vital before administering any type of local anesthetic to a pregnant patient.<ref name="P. 2016"/>

====Recovery====
Permanent nerve damage after a peripheral nerve block is rare. Symptoms are 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. An estimated one in 5,000 to 30,000 nerve blocks results in some degree of permanent persistent nerve damage.<ref name="RoyalCol"/>

Symptoms may continue to improve for up to 18 months following injury.

===Potential side effects===

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 nervous system|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. High plasma levels might arise, for example, when doses intended for [[Epidural administration|epidural]] or intrasupport tissue administration are accidentally delivered as [[intravascular]] injection.{{citation needed|date=October 2018}}<!-- <ref name="Zamanian, R. 2005">Zamanian, R., Toxicity, Local Anesthetics (2005)</ref> -->

==== Emotional reactions ====
When patients are emotionally affected in the form of nervousness or fear, it can lead to vasovagal collapse. This is the anticipation of pain during administration that activates the [[parasympathetic nervous system]] while inhibiting the orthosympathetic nervous system.<ref name=":1">{{Cite book|url=https://books.google.com/books?id=xRgnDwAAQBAJ&q=side+effects|title=Local Anaesthesia in Dentistry| vauthors = Baart JA, Brand HS |date=2017-06-07|publisher=Springer|isbn=9783319437057 }}</ref> What results is a dilation of arteries in muscles which can lead to a reduction in circulating blood volume inducing a temporary shortness of blood flow to the brain. Notable symptoms include restlessness, visibly looking pale, perspiration and possible loss of consciousness. In severe cases, clonic cramps resembling an epileptic insult may occur.<ref name=":1" />

On the other hand, fear of administration can also result in accelerated, shallow breathing, or [[hyperventilation]]. The patient may feel a tingling sensation in hands and feet or a sense of light-headedness and increased chest pressure.{{citation needed|date=February 2022}}

Hence, it is crucial for the medical professional administrating the local anesthesia, especially in the form of an injection, to ensure that the patient is in a comfortable setting and has any potential fears alleviated in order to avoid these possible complications.

==== Central nervous system ====

Depending on local tissue concentrations of local anesthetics, excitatory or depressant effects on the central nervous system may occur.

Initial symptoms of systemic toxicity include ringing in the ears ([[tinnitus]]), a metallic taste in the mouth, tingling or numbness of the mouth, dizziness and/or disorientation.

At higher concentrations, a relatively selective depression of inhibitory neurons results in cerebral excitation, which may lead to more advanced symptoms include motor twitching in the periphery followed by [[Grand Mal seizures|grand mal seizures]]. It is reported that seizures are more likely to occur when bupivacaine is used, particularly in combination with chloroprocaine.<ref name=":2">{{Cite book|url=https://books.google.com/books?id=NYiQYoPjJl4C&q=local+anesthesia+general+side+effects |title=Meyler's Side Effects of Drugs Used in Anesthesia| vauthors = Aronson JK |date=2008-10-07|publisher=Elsevier|isbn=9780444532701|language=en}}</ref>

A profound depression of brain functions may occur at even higher concentrations which may lead to [[coma]], [[respiratory arrest]], and death.<ref name="Mulroy, M. 2002">{{cite journal | vauthors = Mulroy MF | title = Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures | journal = Regional Anesthesia and Pain Medicine | volume = 27 | issue = 6 | pages = 556–561 | date = 2002 | pmid = 12430104 | doi = 10.1053/rapm.2002.37127 | s2cid = 36915462 }}</ref> 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 [[cerebrospinal fluid]], i.e., overdose in spinal anesthesia or accidental injection into the subarachnoid space in epidural anesthesia.

==== Cardiovascular system ====

Cardiac toxicity can result from improper injection of agent into a vessel. Even with proper administration, it is inevitable for some diffusion of agent into the body from the site of application due to unforeseeable anatomical idiosyncrasies of the patient.<ref name=":2" />  This may affect the nervous system or cause the agent to enter into general circulation. However, infections are very seldom transmitted.

Cardiac toxicity associated with overdose of intravascular injection of local anesthetic is characterized by [[hypotension]], [[Atrioventricular node|atrioventricular]] conduction delay, [[Idioventricular rhythm|idioventricular]] rhythms, and eventual cardiovascular collapse. Although all local anesthetics potentially shorten the myocardial refractory period, [[bupivacaine]] blocks the cardiac sodium channels, thereby making it most likely to precipitate malignant [[Heart arrhythmia|arrhythmias]]. Even [[levobupivacaine]] and [[ropivacaine]] (single-enantiomer derivatives), developed to ameliorate cardiovascular side effects, still harbor the potential to disrupt cardiac function.<ref>{{cite journal | vauthors = Stiles P, Prielipp RC |title=Intralipid Treatment Of Bupicavaine Toxicity |journal=Anesthesia Patient Safety Foundation |date=Spring 2009 |volume=24 | issue = 1 |url=http://www.apsf.org/newsletters/html/2009/spring/12_Intralipid.htm |access-date=12 June 2013}}</ref> Toxicity from anesthetic combinations is additive.<ref name=":2" />

==== Endocrine ====
Endocrine and metabolic systems only have slightly adverse effects with most cases being without clinical repercussions.<ref name=":2" />

==== Immunologic allergy ====

Adverse reactions to local anesthetics (especially the esters) are not uncommon, but legitimate [[allergy|allergies]] are very rare. Allergic reactions to the esters is usually due to a sensitivity to their metabolite, [[para-aminobenzoic acid]], and does not result in cross-allergy to amides.<ref name="Dolan, R. 2004">{{cite book | vauthors = Dolan R |title=Facial plastic, reconstructive, and trauma surgery |publisher=Marcel Dekker |isbn=978-0-8247-4595-0|date=2003-10-17 }}</ref><ref name="ReferenceA">Univ. of Wisconsin, Local Anesthesia and Regional Anesthetics</ref> Therefore, amides can be used as alternatives in those patients. Nonallergic reactions may resemble allergy in their manifestations. In some cases, skin tests and provocative challenge may be necessary to establish a diagnosis of allergy. Also cases of allergy to [[paraben]] derivatives occur, which are often added as preservatives to local anesthetic solutions.

==== Methemoglobinemia ====

[[Methemoglobinemia]] is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces [[cyanosis]] and symptoms of [[Hypoxia (medical)|hypoxia]]. Exposure to aniline group chemicals such as  [[benzocaine]], [[lidocaine]], and [[prilocaine]] can produce this effect, especially benzocaine.<ref name="Dolan, R. 2004"/><ref name="ReferenceA"/> The systemic toxicity of prilocaine is comparatively low, but its metabolite, o-toluidine, is known to cause [[methemoglobinemia]].

==== Second-generation effects ====
Application of local anesthetics during oocyte removal during in vitro fertilization has been up to debate. Pharmacological concentrations of anesthetic agents have been found in follicular fluid.<ref name=":2" /> Clinical trials have not concluded any effects on pregnant women. However, there is some concern with the behavioral effects of lidocaine on offspring in rats.<ref name=":2" />

During pregnancy, it is not common for local anesthetics to have any adverse effect on the fetus. Despite this, risks of toxicity may be higher in pregnancy due to an increase in unbound fraction of local anesthetic and physiological changes increase the transfer of local anesthetic into the central nervous system.<ref name=":2" /> Hence, it is recommended that pregnant women use a lower dose of local anesthetic to reduce any potential complications.

====Treatment of overdose: "Lipid rescue"====

'''Lipid emulsion therapy''' or '''lipid rescue''' is a method of toxicity treatment was invented by Dr. Guy Weinberg in 1998, and was not widely used until after the first published successful rescue in 2006. Evidence indicates [[Intralipid]], a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anesthetic overdose, including human case reports.<ref name="Weinberg 1998">{{cite journal | vauthors = Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ | title = Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats | journal = Anesthesiology | volume = 88 | issue = 4 | pages = 1071–1075 | date = April 1998 | pmid = 9579517 | doi = 10.1097/00000542-199804000-00028 | s2cid = 1661916 | doi-access = free }}</ref><ref name="Weinberg 2003">{{cite journal | vauthors = Weinberg G, Ripper R, Feinstein DL, Hoffman W | title = Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity | journal = Regional Anesthesia and Pain Medicine | volume = 28 | issue = 3 | pages = 198–202 | year = 2003 | pmid = 12772136 | doi = 10.1053/rapm.2003.50041 | s2cid = 6247454 }}</ref><ref name="Picard2006">{{cite journal | vauthors = Picard J, Meek T | title = Lipid emulsion to treat overdose of local anesthetic: the gift of the glob | journal = Anaesthesia | volume = 61 | issue = 2 | pages = 107–109 | date = February 2006 | pmid = 16430560 | doi = 10.1111/j.1365-2044.2005.04494.x | s2cid = 29843241 }}</ref><ref name="Rosenblatt2006">{{cite journal | vauthors = Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB | title = Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest | journal = Anesthesiology | volume = 105 | issue = 1 | pages = 217–218 | date = July 2006 | pmid = 16810015 | doi = 10.1097/00000542-200607000-00033 | s2cid = 40214528 | doi-access = free }}</ref><ref name="Litz2006">{{cite journal | vauthors = Litz RJ, Popp M, Stehr SN, Koch T | title = Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion | journal = Anaesthesia | volume = 61 | issue = 8 | pages = 800–801 | date = August 2006 | pmid = 16867094 | doi = 10.1111/j.1365-2044.2006.04740.x | s2cid = 43125067 }}</ref> However, the evidence at this point is still limited.<ref>{{cite journal | vauthors = Cave G, Harvey M | title = Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review | journal = Academic Emergency Medicine | volume = 16 | issue = 9 | pages = 815–824 | date = September 2009 | pmid = 19845549 | doi = 10.1111/j.1553-2712.2009.00499.x | doi-access = free }}</ref>

Though most case reports to date have recorded most common use of Intralipid, other emulsions, such as [[Liposyn]] and [[Medialipid]], have also been shown effective.{{citation needed|date=April 2023}}

Ample supporting animal evidence<ref name="Weinberg 1998"/><ref name="Weinberg 2003"/> and human case reports show successful use of lipid rescue in this way.<ref name="Rosenblatt2006"/><ref name="Litz2006"/> In the UK, efforts have been made to publicize lipid rescue more widely.<ref name="Picard2006"/> In 2010, lipid rescue had been officially promoted as a treatment of local anesthetic toxicity by the [[Association of Anaesthetists of Great Britain and Ireland]].<ref>{{Cite web |date=December 2010 |title=Management of severe local anaesthetic toxicity |url=https://anaesthetists.org/Search-Results?search=Local%20anaesthetic%20toxicity |access-date=2023-04-10 |website=anaesthetists.org. [[Association of Anaesthetists of Great Britain and Ireland]] (AAGBI).}}</ref> One published case has been reported of successful treatment of refractory [[cardiac arrest]] in [[bupropion]] and [[lamotrigine]] overdose using lipid emulsion.<ref>{{cite journal | vauthors = Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB, Weinberg GL, Henretig FM | display-authors = 6 | title = Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine | journal = Annals of Emergency Medicine | volume = 51 | issue = 4 | pages = 412–5, 415.e1 | date = April 2008 | pmid = 17766009 | doi = 10.1016/j.annemergmed.2007.06.004 }}</ref>

The design of a 'homemade' lipid rescue kit has been described.<ref>{{Cite web |title=lipidrescue - Sample LipidRescue Kit |url=http://lipidrescue.squarespace.com/sample-lipidrescue-kit |url-status=live |archive-url=https://web.archive.org/web/20220725082408/http://lipidrescue.squarespace.com/sample-lipidrescue-kit |archive-date=2022-07-25 |website=lipidrescue.squarespace.com}}</ref>

Although lipid rescue mechanism of action is not completely understood, the added lipid in the blood stream may act as a sink, allowing for the removal of lipophilic toxins from affected tissues. This theory is compatible with two studies on lipid rescue for clomipramine toxicity in rabbits<ref name="Harvey 2007">{{cite journal | vauthors = Harvey M, Cave G | title = Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity | journal = Annals of Emergency Medicine | volume = 49 | issue = 2 | pages = 178–85, 185.e1–4 | date = February 2007 | pmid = 17098328 | doi = 10.1016/j.annemergmed.2006.07.016 }}</ref><ref name="Harvey 2009">{{cite journal | vauthors = Harvey M, Cave G, Hoggett K | title = Correlation of plasma and peritoneal diasylate clomipramine concentration with hemodynamic recovery after intralipid infusion in rabbits | journal = Academic Emergency Medicine | volume = 16 | issue = 2 | pages = 151–156 | date = February 2009 | pmid = 19133855 | doi = 10.1111/j.1553-2712.2008.00313.x | doi-access = free }}</ref> and with a clinical report on the use of lipid rescue in veterinary medicine to treat a puppy with [[moxidectin]] toxicosis.<ref name="Crandell 2009">{{cite journal | vauthors = Crandell DE, Weinberg GL | title = Moxidectin toxicosis in a puppy successfully treated with intravenous lipids | journal = Journal of Veterinary Emergency and Critical Care | volume = 19 | issue = 2 | pages = 181–186 | date = April 2009 | pmid = 19691569 | doi = 10.1111/j.1476-4431.2009.00402.x | url = https://zenodo.org/record/898154 }}</ref>

== Mechanism of action ==
All LAs are [[Plasma membrane|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, though it has LA properties).
LA drugs act mainly by inhibiting [[sodium]] influx through sodium-specific [[ion channel]]s in the [[neuron]]al [[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 [[base (chemistry)|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. This is exemplified by the permanently ionised LA [[RAC 421-II]] which cannot [[diffusion|diffuse]] across the cell membrane but, if injected into the cytosol of a nerve fibre, can induce NaKATPase blockage and anesthetic effects.

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.

===Sensitivity of nerve fibers to local anesthetics===
For most patients, administration of local anesthetics causes the sensation of pain to be lost first, followed by temperature, touch, deep pressure, and finally motor function.<ref name=Catterall2023>{{cite book | vauthors = Catterall WA, Mackie K | date = 2023 | chapter = Local Anesthetics | veditors = Brunton LL, Knollmann BC | title = Goodman & Gilman's: The Pharmacological Basis of Therapeutics | edition = 14th | publisher = McGraw Hill | chapter-url = https://accessanesthesiology.mhmedical.com/content.aspx?bookid=3191&sectionid=268045025 | isbn =  978-1-264-25807-9 }}</ref> The sensitivity of nerve fibers to blockade depends on a combination of diameter and myelination. Their different sensitivities to LA blockade is termed differential blockade. Myelinated fibers are more sensitive to blockade as they are interrupted by [[nodes of Ranvier]], thus interruption of only consecutive nodes of Ranvier will prevent action potential propagation. In turn, in unmyelinated nerves, an entire length needs to be blocked.<ref name=Piehl2015>{{cite book | vauthors = Piehl E, Bucklin BA | date = 2015 | chapter = Drugs commonly used in obstetric anesthesia. | veditors = Santos AC, Epstein JN, Chaudhuri K | title = Obstetric Anesthesia | publisher = McGraw Hill | chapter-url = https://accessanesthesiology.mhmedical.com/content.aspx?bookid=1364&sectionid=82007590 | isbn = 978-0-07-178613-3 }}</ref> Regarding diameter, the generally accepted principle is that susceptibility to local anesthesia depends inversely on fiber diameter.<ref name=Gretchen2001>{{cite journal | vauthors = Henkel G | title = Susceptibility of Nerve Fibers to Local Anesthesia:"Size Principle" Challenged. | journal = The Journal of the American Society of Anesthesiologists | date = December 2001 | volume = 95 | issue = 6 | pages = 5A–6A | doi = 10.1097/00000542-200112000-00003 }}</ref>

In general, autonomic fibers [[Group B nerve fiber|Type B fibers]], small unmyelinated [[Group C nerve fiber|type C]] (pain sensation), and small myelinated [[Group A nerve fiber|Aδ fibers]](pain and temperature sensations) are blocked before the larger myelinated Aγ, Aβ, and Aα fibers (mediating postural, touch, pressure, and motor information).<ref  name=Catterall2023/>

== Techniques ==
Local 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 merge into the central nervous system.

Injection of LAs is often painful.  A number of methods can be used to decrease this pain, including buffering of the solution with bicarbonate and warming.<ref>{{Cite web|url=https://bestbets.org/bets/bet.php?id=1480|title=BestBets: The Effect of Warming Local anesthetics on Pain of Infiltration|website=bestbets.org}}</ref>

Clinical techniques include:
* Surface anesthesia is the application of an LA 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 is [[injection (medicine)#Infiltration|infiltration]] of LA into the tissue to be anesthetized; surface and infiltration anesthesia are collectively topical anesthesia
* Field block is subcutaneous injection of an LA in an area bordering on the field to be anesthetized.
* [[Peripheral nerve block]] is injection of LA in the vicinity of a peripheral nerve to anesthetize that nerve's area of innervation.
* Plexus anesthesia is injection of LA 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 is an LA 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 is an LA 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) is when blood circulation of a limb is interrupted using a tourniquet (a device similar to a blood-pressure cuff), then a large volume of LA 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 includes intrapleural anesthesia and intra-articular anesthesia.
{{anchor|catheter anesthesia}}
* Transincision (or transwound) catheter anesthesia uses a multilumen catheter inserted through an incision 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 wounds<ref>{{cite journal | vauthors = Kampe S, Warm M, Kasper SM, Diefenbach C | title = Concept for postoperative analgesia after pedicled TRAM flaps: continuous wound instillation with 0.2% ropivacaine via multilumen catheters. A report of two cases | journal = British Journal of Plastic Surgery | volume = 56 | issue = 5 | pages = 478–483 | date = July 2003 | pmid = 12890461 | doi = 10.1016/S0007-1226(03)00180-2 }}</ref>

Dental-specific techniques include:

=== Vazirani–Akinosi technique ===
The Vazirani–Akinosi technique is also known as the closed-mouth mandibular nerve block. It is mostly used in patients who have limited opening of the mandible or in those that have trismus; spasm of the muscles of mastication. The nerves which are anesthetised in this technique are the inferior alveolar, incisive, mental, lingual and mylohyoid nerves.

Dental needles are available in two lengths, short and long. As Vazirani–Akinosi is a local anesthetic technique which requires penetration of a significant thickness of soft tissues, a long needle is used. The needle is inserted into the soft tissue which covers the medial border of the mandibular ramus, in region of the inferior alveolar, lingual and mylohyoid nerves. The positioning of the bevel of the needle is very important as it must be positioned away from the bone of the mandibular ramus and instead towards the midline.<ref name="Malamed_2013">{{cite book|title=Handbook of local anesthesia| vauthors = Malamed SF |date=2013|publisher=Elsevier|isbn=9780323074131|edition=6th|location=St. Louis, Missouri|oclc=769141511|name-list-style=vanc}}</ref>

=== Intraligamentary Infiltration ===
Intraligamentary infiltration, also known as periodontal ligament injection or intraligamentary injection (ILI), is known as "the most universal of the supplemental injections". ILIs are usually administered when inferior alveolar nerve block techniques are inadequate or ineffective.<ref>{{cite journal | vauthors = Meechan JG | title = Intraligamentary anaesthesia | journal = Journal of Dentistry | volume = 20 | issue = 6 | pages = 325–332 | date = December 1992 | pmid = 1452871 | doi = 10.1016/0300-5712(92)90018-8 }}</ref> ILIs are purposed for:

# Single-tooth anesthesia
# Low anesthetic dose
# Contraindication for systemic anesthesia
# Presence of systemic health problems<ref>{{cite journal | vauthors = Blanton PL, Jeske AH | title = The key to profound local anesthesia: neuroanatomy | journal = Journal of the American Dental Association | volume = 134 | issue = 6 | pages = 753–760 | date = June 2003 | pmid = 12839412 | doi = 10.14219/jada.archive.2003.0262 }}</ref>

ILI utilization is expected to increase because dental patients prefer fewer soft tissue anesthesia and dentists aim to reduce administration of traditional inferior alveolar nerve block (INAB) for routine restorative procedures.<ref>{{cite web | vauthors = Boynes SG | title = Intraligamentary Injections in Dentistry | url = https://www.dentalacademyofce.com/courses/3580%2FPDF%2F1807cei_Boynes_web.pdf | publisher = Dental Academy of Continuing Education | date = 1 June 2018}}</ref>

Injection methodology: The periodontal ligament space provides an accessible route to the cancellous alveolar bone, and the anesthetic reaches the pulpal nerve via natural perforation of intraoral bone tissue.<ref>{{cite journal | vauthors = Meechan JG | title = Supplementary routes to local anaesthesia | journal = International Endodontic Journal | volume = 35 | issue = 11 | pages = 885–896 | date = November 2002 | pmid = 12453016 | doi = 10.1046/j.1365-2591.2002.00592.x }}</ref><ref>{{cite journal | vauthors = D'Souza JE, Walton RE, Peterson LC | title = Periodontal ligament injection: an evaluation of the extent of anesthesia and postinjection discomfort | journal = Journal of the American Dental Association | volume = 114 | issue = 3 | pages = 341–344 | date = March 1987 | pmid = 3470356 | doi = 10.14219/jada.archive.1987.0080 }}</ref>

Advantages of ILI over INAB: rapid onset (within 30 seconds), small dosage required (0.2–1.0&nbsp;mL), limited area of numbness,<ref>{{cite journal | vauthors = Shastry SP, Kaul R, Baroudi K, Umar D | title = Hemophilia A: Dental considerations and management | journal = Journal of International Society of Preventive & Community Dentistry | volume = 4 | issue = Suppl 3 | pages = S147–S152 | date = December 2014 | pmid = 25625071 | pmc = 4304051 | doi = 10.4103/2231-0762.149022 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Nazif M | title = Local anesthesia for patients with hemophilia | journal = ASDC Journal of Dentistry for Children | volume = 37 | issue = 1 | pages = 79–84 | date = January 1970 | pmid = 4904493 }}</ref> lower intrinsic risks such as neuropathy, hematoma, trismus/jaw sprain<ref>{{cite journal | vauthors = Moore PA, Haas DA | title = Paresthesias in dentistry | journal = Dental Clinics of North America | volume = 54 | issue = 4 | pages = 715–730 | date = October 2010 | pmid = 20831934 | doi = 10.1016/j.cden.2010.06.016 }}</ref><ref name = shabazfar>{{cite journal | vauthors = Shabazfar N, Daubländer M, Al-Nawas B, Kämmerer PW | title = Periodontal intraligament injection as alternative to inferior alveolar nerve block--meta-analysis of the literature from 1979 to 2012 | journal = Clinical Oral Investigations | volume = 18 | issue = 2 | pages = 351–358 | date = 2014 | pmid = 24077785 | doi = 10.1007/s00784-013-1113-1 | s2cid = 9525498 }}</ref> and self-inflicted periodontal tissue injury,<ref>{{cite journal | vauthors = Nelson PW | title = Injection system | journal = The Journal of the American Dental Association | date = November 1981 | volume = 103 | issue = 5 | pages = 692 | doi = 10.14219/jada.archive.1981.0380 }}</ref><ref name="pmid6439659">{{cite journal | vauthors = Galili D, Kaufman E, Garfunkel AA, Michaeli Y | title = Intraligamentary anesthesia--a histological study | journal = International Journal of Oral Surgery | volume = 13 | issue = 6 | pages = 511–6 | date = December 1984 | pmid = 6439659 | doi = 10.1016/s0300-9785(84)80022-8  }}</ref> as well as decreased cardiovascular disturbances.<ref>{{cite journal | vauthors = Pashley D | title = Systemic effects of intraligamental injections | journal = Journal of Endodontics | volume = 12 | issue = 10 | pages = 501–504 | date = October 1986 | pmid = 3465856 | doi = 10.1016/s0099-2399(86)80206-0 }}</ref> Its usage as a secondary or supplementary anesthesia on the mandible has reported a high success rate of above 90%.<ref>{{cite journal | vauthors = Walton RE, Abbott BJ | title = Periodontal ligament injection: a clinical evaluation | journal = Journal of the American Dental Association | volume = 103 | issue = 4 | pages = 571–575 | date = October 1981 | pmid = 6945341 | doi = 10.14219/jada.archive.1981.0307 }}</ref><ref>{{cite journal | vauthors = Smith GN, Walton RE, Abbott BJ | title = Clinical evaluation of periodontal ligament anesthesia using a pressure syringe | journal = Journal of the American Dental Association | volume = 107 | issue = 6 | pages = 953–956 | date = December 1983 | pmid = 6581222 | doi = 10.14219/jada.archive.1983.0357 }}</ref>

Disadvantages: Risk of temporary periodontal tissue damage, likelihood of bacteriemia and endocarditis for at-risk populations,<ref name=":4">{{cite journal | vauthors = Roberts GJ, Holzel HS, Sury MR, Simmons NA, Gardner P, Longhurst P | title = Dental bacteremia in children | journal = Pediatric Cardiology | volume = 18 | issue = 1 | pages = 24–27 | date = January 1997 | pmid = 8960488 | doi = 10.1007/s002469900103 | s2cid = 7178684 }}</ref> appropriate pressure and correct needle placement are imperative for anesthetic success, short duration of pulpal anesthesia limits the use of ILIs for several restorative procedures that require longer duration,<ref name=":4" /> postoperative discomfort, and injury on unerupted teeth such as enamel hypoplasia and defects.

Technique description:
* All plaque and calculus to be eradicated, optimally before the operative visit to assist gingival tissue healing.
* Before injection, disinfect gingival sulcus with 0.2% chlorhexidine solution.<ref>{{cite journal | vauthors = Kaufman E, Galili D, Garfunkel AA | title = Intraligamentary anesthesia: a clinical study | journal = The Journal of Prosthetic Dentistry | volume = 49 | issue = 3 | pages = 337–339 | date = March 1983 | pmid = 6573480 | doi = 10.1016/0022-3913(83)90273-1 }}</ref>
* Administration of soft tissue anesthesia is recommended prior to ILI administration. This helps to enhance patient comfort.
* Needle gauges of sizes 27-gauge short or 30-gauge ultra-short needle are usually utilized.<ref name = "Malamed_1982">{{cite journal | vauthors = Malamed SF | title = The periodontal ligament (PDL) injection: an alternative to inferior alveolar nerve block | journal = Oral Surgery, Oral Medicine, and Oral Pathology | volume = 53 | issue = 2 | pages = 117–121 | date = February 1982 | pmid = 6949113 | doi = 10.1016/0030-4220(82)90273-0 }}</ref>
* The needle is inserted along the long axis, at a 30 degree angle, of the mesial or distal root for single rooted teeth and on the mesial and distal roots of multi-rooted teeth. Bevel orientation toward the root provides easier advancement of the needle apically.<ref name=":5">{{cite journal | vauthors = Meechan JG | title = How to overcome failed local anaesthesia | journal = British Dental Journal | volume = 186 | issue = 1 | pages = 15–20 | date = January 1999 | pmid = 10028738 | doi = 10.1038/sj.bdj.4800006 | s2cid = 6618968 }}</ref>
* When the needle reaches between the root and crestal bone, significant resistance is experience.
* Anesthetic deposition is recommended at 0.2&nbsp;mL, per root or site, over minimally 20 seconds.
* For its success, the anesthetic must be administered under pressure. It must not leak out of the sulcus into the mouth.
* Withdraw needle for minimally 10–15 seconds to permit complete deposition of solution. This can be slower than other injections as there is pressure build-up from the anesthetic administration.
* Blanching of the tissue is observed and may be more evident when vasoconstrictors are used. It is caused by a temporary obstruction of blood flow to the tissue.<ref name=":5" />

Syringes:
* Standard syringes can be used.
* The intraligamentary syringe offers mechanical advantage by using a trigger-grasp or click apparatus to employ a gear or lever that improves control and results in increased force to push the anesthetic cartridge's rubber stopper forward for medication deposition with greater ease.
* C-CLADs (computer controlled local anesthetic delivery devices) can be used. Its usage of computer microprocessors allows for control of fluid dynamics and anesthetic deposition. This minimizes subjective flow rates and variability in pressure. This thereby results in enhanced hydrodynamic diffusion of solution into bone or the target area of deposition,<ref>{{cite journal | vauthors = Walton RE, Garnick JJ | title = The periodontal ligament injection: histologic effects on the periodontium in monkeys | journal = Journal of Endodontics | volume = 8 | issue = 1 | pages = 22–26 | date = January 1982 | pmid = 6948904 | doi = 10.1016/S0099-2399(82)80312-9 }}</ref><ref>{{cite journal | vauthors = Hochman MN, Friedman MJ, Williams W, Hochman CB | title = Interstitial tissue pressure associated with dental injections: a clinical study | journal = Quintessence International | volume = 37 | issue = 6 | pages = 469–476 | date = June 2006 | pmid = 16752703 }}</ref> thus permitting larger amounts of anesthetic solution to be delivered during ILIs without increased tissue damage.<ref>{{cite journal | vauthors = Aggarwal V, Singla M, Miglani S, Kohli S, Sharma V, Bhasin SS | title = Does the volume of supplemental intraligamentary injections affect the anesthetic success rate after a failed primary inferior alveolar nerve block? A randomized-double blind clinical trial | journal = International Endodontic Journal | volume = 51 | issue = 1 | pages = 5–11 | date = January 2018 | pmid = 28370327 | doi = 10.1111/iej.12773 }}</ref><ref>{{cite journal | vauthors = Berlin J, Nusstein J, Reader A, Beck M, Weaver J | title = Efficacy of articaine and lidocaine in a primary intraligamentary injection administered with a computer-controlled local anesthetic delivery system | journal = Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics | volume = 99 | issue = 3 | pages = 361–366 | date = March 2005 | pmid = 15716846 | doi = 10.1016/j.tripleo.2004.11.009 }}</ref><ref>{{cite journal | vauthors = Froum SJ, Tarnow D, Caiazzo A, Hochman MN | title = Histologic response to intraligament injections using a computerized local anesthetic delivery system. A pilot study in mini-swine | journal = Journal of Periodontology | volume = 71 | issue = 9 | pages = 1453–1459 | date = September 2000 | pmid = 11022775 | doi = 10.1902/jop.2000.71.9.1453 }}</ref>

Things to note:
* ILIs are not recommended for patients with active periodontal inflammation.
* ILIs should not be administered at tooth sites with 5&nbsp;mm or more of periodontal attachment loss.

=== Gow-Gates Technique ===
Gow-Gates technique is used to provide anesthetics to the mandible of the patient's mouth. With the aid of extra and intraoral landmarks, the needle is injected into the intraoral latero-anterior surface of the condyle, steering clear below the insertion of the lateral pterygoid muscle.<ref name = "Gow-Gates_1998">{{cite journal | vauthors = Gow-Gates GA | title = The Gow-Gates mandibular block: regional anatomy and analgesia | journal = Australian Endodontic Journal | volume = 24 | issue = 1 | pages = 18–19 | date = April 1998 | pmid = 11431805 | doi = 10.1111/j.1747-4477.1998.tb00251.x }}</ref> The extraoral landmarks used for this technique are the lower border of the ear tragus, corners of the mouth and the angulation of the tragus on the side of the face.<ref name = "Gow-Gates_1998" />

Biophysical forces (pulsation of the maxillary artery, muscular function of jaw movement) and gravity will aid with the diffusion of anesthetic to fill the whole pterygomandibular space. All three oral sensory parts of the mandibular branch of the trigeminal nerve and other sensory nerves in the region will come in contact with the anesthetic and this reduces the need to anesthetise supplementary innervation.<ref name = "Gow-Gates_1998" />

In comparison to other regional block methods of anestheising the lower jaw, the Gow-Gates technique has a higher success rate in fully anesthetising the lower jaw. One study found that out of 1,200 patients receiving injections through the Gow-Gates technique, only 2 of them did not obtain complete anesthesia.<ref name = "Gow-Gates_1998" />

== Types ==
[[File:LA syringe.JPG|thumbnail|right|This LA system is designed to prevent [[needlestick injury]]. A cartridge of LA fits into the disposable needle, which can be locked when not in use and can be separated from the handle.]]
Local anesthetic solutions for injection typically consist of:<ref>{{cite web|title=Allergic Reactions|url=https://www.clevelandclinicmeded.com/medicalpubs/pharmacy/JanFeb2001/allergicreaction.htm|publisher=Cleveland Clinic|access-date=11 April 2014}}</ref>
* 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]]
* [[Buffer solution|Buffer]]

[[Amino esters|Esters]] 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".
Most ester LAs are metabolized by [[Butyrylcholinesterase|pseudocholinesterase]], while amide LAs are metabolized in the liver. This can be a factor in choosing an agent in patients with liver failure,<ref name="isbn0-07-136704-7">{{cite book | vauthors = Stern A |title=Pharmacology: PreTest self-assessment and review |url=https://archive.org/details/pharmacology00arno |url-access=registration |publisher=McGraw-Hill, Medical Pub. Division |location=New York |year=2002 |isbn=978-0-07-136704-2 }}</ref> although since cholinesterases are produced in the liver, physiologically (e.g. very young or very old individual) or pathologically (e.g. [[cirrhosis]]) impaired hepatic metabolism is also a consideration when using esters.

Sometimes, LAs are combined, e.g.:
* [[Lidocaine/prilocaine]] (EMLA, eutectic mixture of local anesthetic)
* Lidocaine/tetracaine (Rapydan)
* [[Topical tac|TAC]]

LA solutions for injection are sometimes mixed with vasoconstrictors ([[combination drug]]) to increase the duration of local anesthesia by constricting the blood vessels, thereby safely concentrating the anesthetic agent for an extended duration, as well as reducing [[hemorrhage]].<ref>{{cite journal | vauthors = Yagiela JA | title = Vasoconstrictor agents for local anesthesia | journal = Anesthesia Progress | volume = 42 | issue = 3–4 | pages = 116–120 | year = 1995 | pmid = 8934977 | pmc = 2148913 }}</ref> Because the vasoconstrictor temporarily reduces the rate at which the systemic circulation removes the local anesthetic from the area of the injection, the maximum doses of LAs when combined with a vasoconstrictor is higher compared to the same LA without any vasoconstrictor. Occasionally, cocaine is administered for this purpose. Examples include:
* [[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]],<sup>1</sup>/<sub>2000</sub> (0.05%, 500&nbsp;[[Parts-per notation#ppm|ppm]], {{frac|1|2}} per mille) adrenaline, 4 or 10% cocaine).

Using LA with vasoconstrictor is safe in regions supplied by [[End artery|end arteries]].
The commonly held belief that LA with vasoconstrictor can cause [[necrosis]] in extremities such as the nose, ears, fingers, and toes (due to constriction of end arteries), is invalidated, since no case of necrosis has been reported since the introduction of commercial lidocaine with epinephrine in 1948.<ref>{{cite journal | vauthors = Nielsen LJ, Lumholt P, Hölmich LR | title = [Local anaesthesia with vasoconstrictor is safe to use in areas with end-arteries in fingers, toes, noses and ears] | journal = Ugeskrift for Laeger | volume = 176 | issue = 44 | pages = 44 | date = October 2014 | pmid = 25354008 }}</ref>

===Ester group===
[[File:Procaine.svg|class=skin-invert-image|thumb|[[Procaine]]]]
* [[Benzocaine]]
* [[Chloroprocaine]]
* [[Cocaine]]
* [[Cyclomethycaine]]
* [[Dimethocaine]] (Larocaine)
* [[Oxybuprocaine]]
* [[Piperocaine]]
* [[Propoxycaine]]
* [[Procaine]] (Novocaine)
* [[Proparacaine]]
* [[Tetracaine]] (Amethocaine)

===Amide group===
[[File:Lidocaine.svg|class=skin-invert-image|thumb|[[Lidocaine]]]]
* [[Articaine]]
* [[Bupivacaine]]
* [[Cinchocaine]] (Dibucaine)
* [[Etidocaine]]
* [[Levobupivacaine]]
* [[Lidocaine]] (Lignocaine)
* [[Mepivacaine]]
* [[Prilocaine]]
* [[Ropivacaine]]
* [[Trimecaine]]

===Naturally derived===
[[File:Tetrodotoxin.svg|class=skin-invert-image|thumb|[[Tetrodotoxin]]]]
* [[Saxitoxin]]
* [[Neosaxitoxin]]
* [[Tetrodotoxin]]
* [[Menthol]]
* [[Eugenol]]
* [[Cocaine]]
* [[Spilanthol]]

Most naturally occurring local anesthetics with the exceptions of menthol, eugenol and cocaine are [[neurotoxin]]s, and have the suffix -toxin in their names.  Cocaine binds the [[intracellular]] side of the channels while saxitoxin, neosaxitoxin and tetrodotoxin bind to the [[extracellular]] side of sodium channels.

== History ==
{{more citations needed section|date=February 2014}}
In [[Peru]], the ancient [[Inca mythology#Deities|Incas]] are believed to have used the leaves of the [[coca|coca plant]] as a local anesthetic in addition to its stimulant properties.<ref name="Boca Raton">{{cite news | vauthors = Gazourian A |title=Cocaine's use: From the Incas to the U.S.|url=https://news.google.com/newspapers?nid=1291&dat=19850404&id=0B1UAAAAIBAJ&pg=6387,881236|access-date=2 February 2014|newspaper=Boca Raton News|date=4 April 1985}}</ref> It was also used for slave payment and is thought to play a role in the subsequent destruction of [[Inca Empire#Coca|Incas culture]] when Spaniards realized the effects of chewing the coca leaves and took advantage of it.<ref name="Boca Raton" /> [[Cocaine]] was first used as a local anesthetic in 1884. The search for a less toxic and less addictive substitute led to the development of the aminoester local anesthetics [[stovaine]] in 1903 and [[procaine]] in 1904. Since then, several synthetic local anesthetic drugs have been developed and put into clinical use, notably lidocaine in 1943, bupivacaine in 1957, and prilocaine in 1959.

The invention of clinical use of local anaesthesia is credited to the Vienna School which included Sigmund Freud (1856-1939), Carl Koller (1857-1944) and Leopold Konigstein (1850–1942). They introduced local anaesthesia, using cocaine, through 'self-experimation' on their oral mucosa before introducing it to animal or human experimentation. The Vienna school first started using cocaine as local anaesthesia in ophthalmology and it was later incorporated into ophthalmologic practice. Dr. Halsted and Dr. Hall, in the United States in 1885 described an intraoral anesthetic technique of blocking the inferior alveolar nerve and the antero-superior dental nerve using 4% cocaine.<ref name="López-Valverde_2014">{{cite journal | vauthors = López-Valverde A, de Vicente J, Martínez-Domínguez L, de Diego RG | title = Local anaesthesia through the action of cocaine, the oral mucosa and the Vienna group | journal = British Dental Journal | volume = 217 | issue = 1 | pages = 41–43 | date = July 2014 | pmid = 25012333 | doi = 10.1038/sj.bdj.2014.546 | doi-access = free }}</ref>

Shortly after the first use of cocaine for topical anesthesia, blocks on peripheral nerves were described. Brachial plexus anesthesia by percutaneous injection through axillary and supraclavicular approaches was developed in the early 20th century. The search for the most effective and least traumatic approach for plexus anesthesia and peripheral nerve blocks continues to this day. In recent decades, continuous regional anesthesia using catheters and automatic pumps has evolved as a method of pain therapy.

Intravenous regional anesthesia was first described by [[August Bier]] in 1908. This technique is still in use and is remarkably safe when drugs of low systemic toxicity such as prilocaine are used.

Spinal anesthesia was first used in 1885, but not introduced into clinical practice until 1899, when August Bier subjected himself to a clinical experiment in which he observed the anesthetic effect, but also the typical side effect of postpunctural headache. Within a few years, spinal anesthesia became widely used for surgical anesthesia and was accepted as a safe and effective technique. Although atraumatic (noncutting-tip) cannulae and modern drugs are used today, the technique has otherwise changed very little over many decades.

Epidural anesthesia by a caudal approach had been known in the early 20th century, but a well-defined technique using lumbar injection was not developed until 1921, when [[Fidel Pagés]] published his article "Anestesia Metamérica". This technique was popularized in the 1930s and 1940s by Achile Mario Dogliotti. With the advent of thin, flexible catheters, continuous infusion and repeated injections have become possible, making epidural anesthesia still a highly successful technique. Besides its many uses for surgery, epidural anesthesia is particularly popular in obstetrics for the treatment of labor pain.

== See also ==
* [[Amylocaine]]
* [[Anesthetic]]
* [[General anesthetic]]
* [[List of cocaine analogues]]
* [[List of local anesthetics]]

== References ==
{{Reflist|30em}}

== External links ==
* [https://www.asra.com/ The American Society of Regional Anesthesia]
* [https://www.asra.com/news-publications/regional-anesthesia-pain-medicine-journal ''Regional Anesthesia & Pain Medicine'']

{{Major drug groups}}
{{Local anesthetics}}
{{Neuropathic pain and fibromyalgia pharmacotherapies}}
{{Anesthesia}}

{{Authority control}}

[[Category:Anesthesia]]
[[Category:Local anesthetics| ]]