Can Lidocaine Cause Skin Rash

• Journal List
• Medicina (Kaunas)
• v.57(eight); 2021 Aug
• PMC8399637

Medicina (Kaunas). 2021 Aug; 57(8): 782.

Lidocaine: A Local Coldhearted, Its Adverse Furnishings and Direction

Enrico Camporesi, Academic Editor

Received 2021 Jul 5; Accustomed 2021 Jul 26.

Abstract

The nearly widely used medications in dentistry are local anesthetics (LA), especially lidocaine, and the number of recorded agin allergic responses, particularly of hazardous responses, is quite low. However, allergic reactions can range from moderate to life-threatening, requiring rapid diagnosis and treatment. This article serves as a review to provide information on LA, their adverse reactions, causes, and management.

Keywords: local anesthetics, lidocaine, adverse allergic responses

1. Introduction

A local anesthetic (LA) is a medicine that is used to numb a small part of the body temporarily before performing a minor surgery like skin biopsy. Before a dental performance, such as tooth extraction, LA may be given to the patient. LA practise non cause humans to fall asleep, unlike general anesthesia. They are commonly distinguished by their chemic structure, specifically the linkage between the compound's common components, such equally amide and esters [1]. The vast majority of the regularly used dental LA are amides, for case, lidocaine, mepivacaine, bupivacaine, etidocaine, prilocaine, and articaine [2]. The maximum recommended dose of LA may vary based on the nation, gender, historic period, weight, and medical status of the patient. The gathering of information from several sources, Table 1 shows the acceptable maximum doses of LA with or without vasoconstrictor [three,4,5].

Table 1

Acceptable maximum dosages of normally used local anesthetics [ii,3,4,5].

Local Anesthetics (LA)	Concentration Available (%)	Maximum Recommended Dose (mg/kg)				* Maximum Recommended Full Dosage (mg)
		Without Vasoconstrictor		With Vasoconstrictor		Adult	Children
		Developed	Children	Adult	Children
Lidocaine	two.0	N/A	4.4	7.0	iv.4	500	300
Mepivacaine	two.0	North/A	4.4	6.half dozen	4.4	400	300
	3.0	6.six	four.iv	N/A	4.4
Bupivacaine	0.5	N/A	N/A	2.0	1.3	175	90
Etidocaine	one.5	4.5	N/A	6.5	N/A	400	300
Prilocaine	4.0	eight.viii	6.0	8.viii	6.0	600	400
Articaine	4.0	N/A	N/A	7.0	7.0	500	500

Lidocaine, also known every bit lignocaine, is a class Ib antidysrhythmic and local amino amide-based anesthetic that has been on the market since 1948 (Figure one) [6,7]. Due to its superior prophylactic profile as compared to other LA agents, it was quickly adopted. It can also exist used to treat acute and chronic hurting as an adjuvant analgesic [8,ix,10]. It is widely used to salve pain later on a pocket-sized surgery or invasive procedures like biopsies, pocket-size excisions, or dental surgery. However, as lidocaine can be used in different means, i.e., by injection, inhalation, or as a topical amanuensis to provide anesthesia to the same patients, it is essential to proceed records of the total dose given to avoid its systemic toxicity. Lidocaine should non exist used in patients with confirmed allergic hypersensitivity to amide-based LA. Due to the increase in the number of over-the-counter (OTC) drugs containing topical amide anesthetics such as lidocaine, the incidence of allergic contact dermatitis (ACD) to LA is ascent. The ACD to LA is mutual, with an incidence of ii.4%, in which 32% of cases are linked to lidocaine [11]. The incidence of lidocaine allergy in 17 subjects out of 100 dentists (assumed patients) was detected, in which type I hypersensitivity was diagnosed in 13 cases, and 4 subjects had an IgE-independent allergy [12]. Sixteen cases of allergy contact dermatitis and delayed hypersensitivity to lidocaine were reported by Antoine et al. [13]. While local anesthetics accept not been linked to serum enzyme elevation, they accept been reported as potential causes of clinically evident liver injury when given as continuous infusions or repeated injections. Poisoning with the parenteral form of lidocaine is the most well-known, although poisoning with a topical spray formulation is also possible [xiv]. Information technology has undesirable effects on the cardiovascular organization (CVS) and the central nervous systems (CNS) in one case ingested in large amounts [fifteen,16,17]. Toxicity to regional nerves and muscles is thought to be caused by long-term employ of loftier drug concentrations, by the presence of preservatives in the amide-based LA solution such every bit lidocaine, or both [xviii,19]. During regional anesthesia, an inadvertent intravascular injection (primarily into the neck) of lidocaine causes severe cardiotoxicity such as hypotension, atrioventricular heart block, idioventricular rhythms, and life-threatening arrhythmias such every bit ventricular tachycardia and fibrillation, which are usually the offset signs of LA toxicity [20]. A case of death of a 32-yr-old male from a lethal dose of lidocaine was reported past Kalin et al. [21]. A case of death of a 76-year-old human with eye disease as a result of an excessive dose of lidocaine was reported [22]. A study regarding acute toxicity of lidocaine with a mortality rate of ten% was reported [7].

Chemical structure of lidocaine.

Antioxidants and preservatives in lidocaine, such as metabisulfite and parabens, may trigger allergic or adverse reactions in some people [23,24]. The most mutual allergic reaction is acquired by the ester's metabolic product, para-aminobenzoic acid, as cross-reactivity between esters is common [25]. By causing percutaneous and mayhap ingestive sensitivity, parabens can cause allergic responses [26].

Parabens are a category of preservatives that is widely used in ointments, cosmetics, creams, lotions, dentifrices, toiletries, foods, and local anesthetics to inhibit the growth of microbes [27]. They are alkyl esters (methyl, ethyl, propyl, or butyl) of p-hydroxybenzoic acid, a chemical compound present in many fruits and plants that occurs naturally [28]. Its phenol-like activity, which probably works by poly peptide denaturation and the antimetabolite properties of p-hydroxybenzoic acid, has shown bacteriostatic, fungistatic, and oxidant properties [29]. Chemical structures (Effigy 2) and actions of the commonly used parabens are very like, with the "R" group irresolute as shown in Tabular array 2. The nearly widely used parabens are methylparaben, ethylparaben, propylparaben, and butylparaben, while many parabens (isopropyl-, isobutyl-, pentyl-, phenyl-, benzyl-) have been used, too.

Common chemical structure of parabens.

Tabular array ii

Chemical construction of dissimilar parabens.

Substance	R
Para-hydroxybenzoic acid	-H
Methylparaben	-CH3
Ethylparaben	-CH2CH3
Propylparaben	-CH2CHtwoCH3
Butylparaben	-CH2CHii CH2CH3
Benzylparaben	-CH2 C6H5

The LA solutions typically contain 0.one% methylparaben, and the effective concentration is depression (0.1–0.3%). Methylparaben is metabolized to para-aminobenzoic acid (PABA), which is a highly antigenic substance and is near likely a source of allergic reactions [30,31,32]. One of the most regularly used parabens, methylparaben, has been linked to T cell-mediated sensitivity, with urticarial maculopapular rash [33,34,35]. Microscopic examination of pare revealed balmy-to-severe dermal inflammation and hyperkeratosis with acanthosis afterwards iii months of exposure to a product containing 0.ii% methylparaben and 0.2% propylparaben in rabbits [26]. However, information technology remains poorly known whether parabens used in LA solutions are truly a source of allergic reactions.

Scientists have worked tirelessly to increment the efficacy and reduce the adverse reactions connected with lidocaine. Despite the fact that allergic reactions to lidocaine are quite rare, they tin be true. Notably, patients who are allergic to lidocaine cause a claiming to the dentist in terms of delivering adequate handling and managing postoperative pain [36]. Moreover, the acceptable limit for the incidence of true allergies to lidocaine is below one%, and so practitioners must be trained and educated properly in guild to manage and diagnose a true LA allergic reaction [37]. Unfortunately, lack of awareness of agin reactions to LA as well every bit the lack of allergy testing, diagnosis, and direction has resulted in unavoidable dental consequences. Therefore, our review aims to provide informative descriptions regarding LA, their adverse reactions, causes, allergy testing, diagnosis, and management.

2. Identifying Allergic Reactions in Adverse Events

2.1. Fright or Anxiety-Related Adverse Reactions

Unintended intravenous assistants of LA, poisonous overdose, sensitivity, and idiosyncrasy may all be misinterpreted as true allergic reactions [38]. Toxic side effects of local anesthetics are caused past either systemic exposure or a local pharmacologic consequence [39]. Potential precipitating factors include irrational needle fears, chair posture, liver or kidney dysfunction, maximum prescribed doses, adequate condom precautions, and concurrent drug interactions. The easiest and most effective way for detecting take chances factors that can lead to an agin incident is to take a detailed medical history [40]. When adverse effects occur, the provider's familiarity with the patient is critical as it allows for quick diagnosis and successful intendance [41].

ii.2. Psychogenic Effects

In dentistry, anxiety plays a significant role. It has been reported that a substantial portion of the population in the United States is condign more than worried well-nigh dental care [42]. The most common adverse events seen in a dental role are psychogenic effects. These psychogenic responses are often misdiagnosed as allergic reactions due to their similarities.

ii.iii. Allergic Reactions

The common symptoms of allergic reactions include anaphylaxis, urticaria, edema, bronchospasm, unconsciousness, hyperventilation, nausea, airsickness, and changes in heart rate or blood pressure [43].

It is important to know the distinctions betwixt allergic and psychogenic reactions so that patients get the treatment they need [44,45].

iii. Response to Allergies

Originally, the immune response organization of the body was thought to exist solely protective; yet, extreme allergic reactions' dangerous potentials were gradually discovered. Hypersensitivities, as well known equally allergies, are incredibly active immune responses in which the allowed arrangement destroys tissue when fighting a possible risk, or an antigen, which would otherwise be prophylactic to the individual. A instance of sudden expiry after a gingival injection of lidocaine was reported, with suspected overdosing or anaphylactic stupor [46]. These reactions can range in severity from balmy to life-threatening, and the clinical manifestations of an antigen reaction can range from balmy (with minor skin manifestations over time) to those requiring firsthand diagnosis and aggressive handling to avert respiratory and cardiovascular collapse which tin can lead to death. An allergic reaction occurred 30 min after a local infusion of lidocaine for the retraction of retained teeth in an 86-year-one-time woman [47]. There are several forms of hypersensitivity reactions, which are better categorized based on the disease's immunologic mechanism (Table 3).

Table 3

Several forms of hypersensitivity reactions accelerated past local anesthetics and their management [48,49].

Hypersensitivity Reaction	Mechanism	Associated Disorder	Signs and Symptoms	Management
Mild allergy	Bodily histamine release response	Skin rash not associated with respiratory or cardiovascular issues	Itching, hives, and/or rash	Administration of a histamine blocker such as diphenhydramine by the intramuscular (IM), intravenous (Four), or oral road
Anaphylactic	Increased vascular permeability, edema, and smooth muscle hyperreactivity are all caused by IgE-sensitized mast cell mediators	Anaphylaxis, bronchial asthma, urticaria	A mild-to-moderate rash, erythema, or urticaria on the pare, swelling of the airways, erythema, pruritus, and edema, with or without angioedema, hypotension, tachycardia, dyspnea, gastrointestinal disturbances, severe bronchospasm, cardiac dysrhythmias, and cardiovascular collapse	Early on administration of epinephrine (IM), maintenance of the airways and ventilation with 100% oxygen, positive pressure ventilation via a bag-valve-mask device, advanced airway adjuncts (e.g., supraglottic airways, endotracheal)
Anaphylactoid	Triggers the release of a combination of biochemical mediators, such as histamine, neutral proteases, prostaglandins, leukotrienes, and other chemokines and cytokines

4. Allergy Testing Procedures

A detailed account of the incidents equally well as a thorough review of the history of a recorded allergic reaction is needed. The drugs used, the onset of the reaction, signs and symptoms, and the elapsing of the outbreak are all essential factors to consider when diagnosing a true allergic reaction. The majority of the reported adverse reactions are psychological, with only a pocket-size per centum caused past an avoidable intravascular injection. It is important not to label a patient every bit allergic besides quickly; instead, the true nature of the problem should be investigated. If the reaction is serious and conspicuously indicates an allergic reaction, a referral to an allergist is considered standard of care [l]. To assist in the pick of a safe local coldhearted for a particular patient, allergists use skin prick tests (SPTs), intradermal or subcutaneous positioning tests, and/or drug provocative challenge testing (DPT) procedures.

Typically, an SPT is conducted, which involves softly pricking the peel with a plastic applicator to inject a minor quantity of an LA solution. The arm is used for this exam, and a crimson raised itchy hive emerges on the skin within fifteen–twenty min due to LA sensitivity [29]. If an allergic reaction takes identify, the required allergic reaction treatment protocol must exist implemented. If the test is carried out with a highly diluted agent and the results are negative, a more than concentrated amanuensis could be used [51]. If the SPT is negative, an intracutaneous or intradermal test, in which a pocket-size corporeality of the test solution is injected into the epidermis of the forearm and the site is examined for 20 min for wheal or flare reactions, is sufficient. Subcutaneous provocation testing begins with 0.i mL of the undiluted local anesthetic solution followed by 0.2, 0.five, ane.0, and two.0 mL into the extensor side of the patient's upper arm at thirty-min intervals if the prick and intradermal tests are negative [52]. Merely if the example history, pare exam, and the laboratory exam yield cryptic results, DPT with the substance in question is performed [53]. Many allergists regard DPT as the golden standard in the diagnosis of drug allergies; nevertheless, there is concern about the test'southward potential side effects [54]. Before beginning any DPT, an individual run a risk-benefit analysis should be completed, and strict surveillance with emergency protocols should be implemented. In general, the clinician should start with a low dose and gradually increase it, discontinuing administration as before long equally any signs or symptoms ascend [54]. The effectiveness of this procedure is dependent on the extremely rare occurrence of a true allergic reaction to amide-based local anesthetics; however, the testing relieves stress for both the patient and the doctor, and it may enable diagnosis of the extremely rare amide allergy [54].

Unfortunately, in that location is no reliable in vitro allergy screening procedure that can exist used on a regular basis. Gall et al. used a cocky-made radioallergosorbent exam with polystyrene discs and a local anesthetic, but all of the patients were negative [55].

5. Management of Agin Reactions

5.1. Firsthand Management

5.1.1. General Considerations

Local anesthetic systemic toxicity (Final) is an essential side consequence to be aware of, ranging from minor symptoms to serious cardiac or central nervous system (CNS) bug. The following guidelines should be followed in general for the management of toxic reaction of LA [iii].

• (a)

  Treatment should be customized for the affected person.

• (b)

  The patient should be lie in the supine position, with the face and torso facing upward, with extended legs, and injuries should be avoided.

• (c)

  Basic life support, ABCs (airway, breathing, and circulation/compression) should exist supplied equally required.

• (d)

  If a seizure lasts more than a few minutes, oxygen should be given.

• (eastward)

  In case of persistent seizures, an effective anticonvulsant should be explored, for case, a benzodiazepine, diazepam, thiopental, etc.

• (f)

  Adequate observation followed past direction of the signs and symptoms equally required (such every bit hypotension, apnea, and cardiovascular collapse).

The kickoff line of defense against Terminal should be airway management, circulatory support, and fugitive systemic side events. Quick breathing and oxygenation tin help with resuscitation and reduce the danger of seizures and cardiovascular collapse. LAST is addressed symptomatically with pharmacologic therapies such every bit benzodiazepines, barbiturates, or propofol, which raise the seizure threshold. Hyperventilation (loftier-dose oxygen) reduces the cerebral blood flow and has been used to improve the seizure threshold [56,57].

The introduction of lipid emulsions reduces the plasma concentration of free accessible LA, which is the other premise of handling. The infusion of lipid emulsions binds gratis circulating local anesthetics and lowers plasma levels due to their loftier lipid solubility. The American Society of Regional Anesthesia and Hurting Medicine (ASRA) publish its management recommendations concerning LAST on a regular basis to reflect new information, user input, and simulation [58,59,60,61,62]. Effigy three reflects a part of a clinical organization for managing Concluding suggested by the American Gild of Regional Anesthesia and Pain Medicine (ASRAPM).

The American Gild of Regional Anesthesia and Pain Medicine (ASRAPM) guidelines for the management of local coldhearted systemic toxicity (LAST) [59,60].

Successful outcomes have been reported fifty-fifty after prolonged resuscitation, which may be explained in office by suggestions in animate being models that bupivacaine, when added to a cardioplegia solution, really improves the function and reduces cellular damage of isolated rat hearts afterwards prolonged cold storage.

five.i.two. Pharmacotherapy Management of Anaphylaxis/Anaphylactoid Reactions

Epinephrine is the primary and first medicine of choice in the treatment of anaphylaxis because it has the ability to sustain claret pressure while also relaxing bronchial smooth muscles. Furthermore, epinephrine efficiently counteracts the negative effects of circulating mediators [63]. In anaphylaxis, in that location is no known dosage or regimen for intravenous (Four) epinephrine. Due to the take chances of potentially fatal arrhythmias, epinephrine should only be given Four during cardiac arrest or to greatly hypotensive patients who have failed to respond to 4 volume replacement and many intramuscular (IM) epinephrine injections (Table 4) [48].

Tabular array iv

Pharmacotherapy management of anaphylaxis/anaphylactoid reactions [48,64,65,66].

Treatment	Medications		Dose (mg/kg)	Route of Assistants	Site of Administration
Primary treatment	Epinephrine		0.3	IM	Deltoid or vastus lateralis
			0.05–0.ii	IV	Blood
Secondary treatment	Bronchodilator (β2-agonist)	Albuterol	0.09	Inhalation	Nasal
	H1-blocker (antihistamine)	Diphenhydramine	0.5	Four	Blood
	Optional
	H2-blocker	Famotidine (Pepcid)	20	Four	Blood
	Steroids	Hydrocortisone	1–2.five	IV	Blood
		Methylprednisolone	1	Iv	Claret

5.ii. Preparations without Preservatives

Patients that are resistant to ester-based local anesthetics should be treated with a preservative-costless amide-based local coldhearted, whether based on medical history or intradermal skin testing. To prevent an allergic reaction to the PABA metabolite of methylparaben, a preservative agent, an amide-based local coldhearted without preservatives should exist selected.

v.3. Antihistamines

Antihistamines accept a chemic human relationship with caine-blazon local anesthetics, which may clarify how they role as local anesthetics. Rosenthal and Minard discovered in 1939 that diphenhydramine induced local anesthesia that was equivalent to that produced by ane% procaine [67,68]. Despite the manufacturer's warning against using diphenhydramine as a local anesthetic, multiple reports of its usage in dental and pocket-size surgical procedures have appeared in the literature since and then [67,68,69,70]. Diphenhydramine has a longer onset and shorter time of action than lidocaine. With diphenhydramine, fewer patients report achieving complete anesthesia [67,68,69,70].

five.four. Epinephrine

Epinephrine is an alpha/beta agonist that is used in LA cartridges every bit an adjuvant. Epinephrine is also used as a starting time-aid medication for anaphylaxis and as a vasoconstrictor to reduce systemic absorption of LA and prolong the duration of anesthetic activity. Table 5 presents the formulations of LA containing epinephrine bachelor in cartridges.

Table five

Ratio of local anesthetics (LA) and epinephrine available in cartridges [2,4,v,71].

Local Anesthetics (LA)	Formulation (LA: Epinephrine)		Maximum Recommended Dose (mg/kg)		* Maximum Recommended Total Dosage (mg)
	Adult	Children	Adult	Children	Adult	Children
Lidocaine, ii%	ane:50,000, one:100,000	1:50,000, 1:100,000	7	4.iv	500	300
Bupivacaine, 0.5%	1:200,000	1:200,000	two	i.iii	175	90
Prilocaine, 4%	1:200,000	1:200,000	8.8	6	600	400
Articaine, 4%	i:100,000, 1:200,000	1:100,000	seven	7	500	500

five.5. General Analgesia and Hypnosis

In patients who have hypersensitivity reactions to local anesthetics, general analgesia, such every bit inhaled nitrous oxide (N20), is an option. For certain patients, intravenous opioids may provide adequate analgesia during labor. In example of potential hypersensitivity to LA and in patients who have autonomic responses to local anesthetic administration, hypnosis is especially useful [72].

half dozen. Conclusions

True allergic reactions to LA are rare adverse events with unexpected outcomes, but effective therapy can save a patient'south life. If a probable allergic reaction occurs, the dentist must appraise the events that have led up to the reaction and make a treatment program. For proper diagnosis, the dentist must follow scientific guidelines for the management of allergic reactions discussed in this minireview.

Acknowledgments

Not applicable for this study.

Writer Contributions

Eastward.B.: conceptualization, methodology, data curation, software, formal analysis, writing—original draft training; H.Y.: supervision, validation, investigation, resources, project administration, funding acquisition, writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by the Basic Science Inquiry Program through the National Research Foundation of Korea (NRF), funded by the Ministry building of Science and ICT (2019R1FA1059148).

Institutional Review Board Statement

Not applicative for this study.

Informed Consent Statement

Not applicable for this study.

Data Availability Statement

The data presented in this study are available in this article in Medicina.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

Publisher'southward Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399637/

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