Editing Local anesthetic (section)

== 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>