In-office dermatological procedures are usual and include from the biopsy of minor injuries to cosmiatric procedures and long complex surgeries. Local anesthesia is essential for the viability of, and good tolerance to, their conduction. This method is safe and recommended for most procedures performed outside the out- and inpatient environment.1,2 The aim of the present study was to make a literature review about the safety of applying local anesthetics with emphasis on adverse reactions.

The methodology used to select the articles was based on the PICO method (Problem/Patient/Population, Intervention/Indicator, Comparison and Outcome). Patients subjected to dermatological procedures composed the population of the present study, local anesthetics were the intervention and the adverse reactions were the outcomes – the comparison group was not determined.

Results in this review were divided into the following subtitles: Action mechanisms of local anesthetics, Classification and pharmacokinetics, Types of local anesthetics, Adverse reactions, Application techniques, Safety of anesthetics and Special situations.

Pain sensation depends on the ability of the nervous system to transmit electrical impulses. This propagation occurs due to different electrolyte concentrations between the intracellular region – which presents high potassium concentration (K+) and lower sodium concentrations (Na+) – and the extracellular region, where concentrations are reversed. This ionic gradient is kept by the sodium-potassium adenosine triphosphatase (Na+ K+ ATPase) pump. The external membrane of the nerve (at rest) presents positive load in comparison to the internal region due to the low membrane permeability to Na+ and to the action of the pump, which excludes three Na+ ions for each of the two internalized K+ ions.3,4

The membrane becomes permeable to the Na+ accumulated inside the cell whenever there is stimulus over the nerve, and this process ends up in depolarization. This change in Na+ permeability also changes the electrical potential through the membrane; the propagation of this electrical potential is called action potential. The nerve returns to the resting state by changing the membrane permeability to Na+ again.3–5

Local anesthetics act in the Na+ K+ ATPase pump, and this process stops the sodium inflow and the propagation of pain stimulus through nervous fibers; thus, it avoids depolarization.2,5

Pain sensation is spread through unmyelinated fibers (Fibers C), which are more sensitive to local anesthetics than myelinated fibers (Fiber A and B). This process allows sensations such as vibration and pressure to remain even after complete pain inhibition.2,5

Local anesthetics are composed of a structure divided into three parts: aromatic group (lipophilic), intermediate chain and amine group (hydrophilic).

The aromatic ring provides lipid solubility to the substance; the higher the solubility, the greater the anesthetic diffusion in the nervous membrane. This property is correlated to the power of the medication.

The terminal amine has the tertiary (liposoluble) and quaternary forms (water soluble). The anesthetic is administered in its quaternary form, and its action occurs according to the proportion of molecules that turn into the tertiary form after getting in contact with the physiological pH (7.4). The ionization constant (pKa) of the anesthetic represents the pH, and half of the molecules are found in their tertiary form, and the other half is in the quaternary form. Most anesthetics have pKa similar to the physiological pH (7.4). The acidified environment favors the quaternary form whenever there is inflammation; it reduces the amount of anesthetic capable of penetrating the nerves.5

The intermediate chain can be composed of ester and amide, which are responsible for the anesthetic classification (Table 1).5,6

Amide-type anesthetics are metabolized by the liver and they must be used carefully in patients with kidney issues. Ester-type anesthetics are degraded by plasma pseudocholinesterase and their metabolites are excreted through urine. The Para-Aminobenzoic Acid (PABA) is one of their metabolites, and it is responsible for the risk of developing allergic reactions to this group of medications. Different from what happens with anesthetics in the amide group, the potential for cross reactions between anesthetics in this group is known.3,5,6

The affinity of anesthetics with plasma proteins is correlated to the affinity of such proteins with the transmembrane sodium channels; the greater the affinity, the longer the action time of the anesthetic and its duration (Table 1).5,6

There are different methods to induce local anesthesia: topical, infiltrative, field block, peripheral nerve block and tumescent anesthesia. All these methods have transient regional anesthesia.3,5

Substances in topical anesthesia are administered straight into the skin or into the mucosa through moisturizers, ointments, gels or sprays. Accordingly, the agent penetrates and reaches the papillary dermis to act in the endings of nerve branches.3,5 The composite easily crosses the skin when the pka of the anesthetic gets close to the skin pH (5.5) and the corneal layer is thin (such as in the eyelids) or absent (mucosa).7,8

Infiltrative anesthesia is obtained through medication administration right on the dermis, or through subcutaneous administration, which causes direct inhibition of nerve endings. Action starts right when the substance is injected in the dermis; however, the injection is quite painful. Pain is milder when the substance is injected in the subcutaneous tissue, but the duration time can be shorter due to the absorption of higher amounts of substance.3,5

Field blocking consists in the deposition of anesthetic solution around the desired site (circumference shape) to anesthetize the superficial and deep nerves responsible for the innervations of the target region. Thus, it is possible anesthetizing with less product when there is no distortion in the area to be treated.3,5

In order to block the peripheral nerve, the anesthetic must be injected around the main nerve. This method allows expressive reduction in the necessary volume of anesthetic for the procedure and prevents distortions in the operative site. These methods are broadly used in face, dactyl and nail dermatological procedures, besides demanding detailed knowledge about anatomy and acknowledged professional expertise.3,5

The tumescent anesthesia is similar to the infiltrative one; however, it demands more diluted doses of the substance right in the region to be subjected to the procedure. Due to the lower concentration of anesthetic, one can use a larger volume of it with low toxicity risk. This technique is applied to liposuction, dermabrasion and hair implant.5,9

Local anesthetics are quite safe when they are properly used. However, although rare, they can cause some adverse reactions, including some events with systemic repercussion.

Undesired reactions can be divided into two categories: the ones associated with needle penetration in the skin and the ones associated with the anesthetic solution. Pain, edema, bruise, infection, hyperalgesia and muscular trismus stand out among factors in the first category (needle penetration in the skin).5 Reactions associated with the solution concern local or systemic toxicity, allergic and idiosyncratic reactions.5

The correct anesthetic application technique assures procedure safety and comfort. The doctor must wear gloves and make proper skin antisepsis. The site to be treated must be marked prior to the administration of the anesthetic in order to avoid local distortion due to the volume of injected medication.5

Thin and small needles must be used whenever possible, because they enable less discomfort. Slow infusion, skin vibration, use of warm solution, skin cooling and minimal injections in the skin also help achieving comfort sensation. In some cases, topical anesthetics are recommended to be applied to the skin prior to the injectable anesthetic, mainly in children.1,5

Topical anesthetic must be applied to intact skin, i.e., on skin free from erosion or eczema. It is important avoiding the contact between the medication and the ocular mucosa, as well as the use of anesthetics belonging to the amide group in patients with kidney issues, and the use of EMLA anesthetics in newborns.8

According to the American guidelines published in 2016, local anesthetics are safe medications to be used in in-office dermatological procedures. Systemic toxicity episodes and episodes of anaphylactic reaction to local anesthetic are rare and many authors recommend them for surgical procedures conducted outside the hospital environment.1,2,30–32

The prospective study by Starling et al. (2012) collected data about complications in outpatient procedures in Florida State from 2000 to 2010, and in Alabama State from 2003 to 2009, both in the United States. In Florida, they reported 46 deaths and 263 complications during surgical procedures: 45% of these complications happened during procedures conducted by plastic surgeons. Only four complications happened during procedures conducted by dermatologists, without deaths (1.3% of the cases): one episode of vasovagal reaction after liposuction in patient subjected to general anesthesia; one case of short-duration atrial fibrillation in patient subjected to skin excision; one incorrect surgical excision in Mohs surgery; and one episode of second degree burn in bedridden patient using home oxygen, who was sedated for the dermatological procedure. In Alabama State, they reported 3 deaths and 49 complications during outpatient procedures. Plastic surgery was the medical specialty recording the highest index of complications (42.3% of the cases). Only one complication happened during procedures conducted by dermatologist, and it did not evolve to death; this number corresponds to only 1.3% of the cases: only one patient presented infection caused by methicillin-resistant Staphylococcus aureus after a melanoma excision. There was no complication after cosmetic procedures based on local anesthesia performed by dermatologists.2

The research by Hanke, Bernstein and Bullock included 15,336 patients subjected to liposuction with tumescent anesthesia conducted by dermatological surgeons; their study showed complications in only 0.38% of the cases. Two patients had cardiac arrhythmia and two presented persistent tachycardia. No death was reported.33 Klein and Jeske also showed safe lidocaine serum levels when they used high doses of tumescent anesthesia in patients subjected to liposuction.34

The prospective cohort study by Alam et al. recorded similar results for 19 patients subjected to micrographic Mohs surgery. These authors measured six lidocaine serum levels administered in three different times during a surgical procedure. There was no lidocaine serum level increase at toxic doses, even during procedures that have used higher doses of the anesthetic: the highest lidocaine serum level found by them was 0.3μg/mL.35

In 2012, Walsh and collaborators published a study showing that dermatologists’ knowledge about the doses and toxicity of local anesthetics is satisfactory. However, the treatment applied to systemic toxicity with lipid emulsion was properly informed by 21.7% of the participants in the study, and this index was considered low by the authors.36

The retrospective study by Kvisselgaard and collaborators ruled out hypersensitivity reaction in all 164 patients in their study, who were previously referred to an Allergology and Immunology clinic with the suspicion of type 1 reaction to local anesthetics between 2010 and 2014. These authors believe that this event was rare due to the use of these medications.37

Although adverse reactions to anesthetics are not frequent, doctors must be careful during their use. The selection of the adequate medication, the identification of risk signs and the handing of complications are essential knowledge for dermatologists.6

Local anesthetics can be considered safe medications for use by dermatologists. Although some adverse reactions are considered severe, such as systemic toxicity and anaphylactic reaction, their occurrence is rare. Proper management of these medications, adequate application technique and knowledge about adverse events, and their specific treatment, reduce risks associated with local anesthetics and make their in-office application viable.

On September 18, 2017, new rules for operation in private medical offices, outpatient and hospitals came into force in Brazil. They were published by the Federal Council of Medicine (Conselho Federal de Medicina – CFM) after some changes in Resolution CFM n° 2.056/2013.

Offices or services that perform invasive medical procedures involving the risk for anaphylaxis, and respiratory and cardiovascular failure – including places where only local anesthetics without sedation are used – were kept in Group 3 Dermatology Offices. In this case, besides the basic structure for propaedeutic, these offices and services must have input and equipment for the therapeutics and treatment of anaphylactic reactions, and for immediate relief of complications caused by therapeutic intervention.

According to evidences shown in the present study about the safety profile of local anesthetics for dermatological procedures, the authors suggest a review about the current demands of the resolution in force. Dermatological procedures such as the excision of small cutaneous lesions, which demand safe doses of local anesthetics (<6.4mL of lidocaine)20 and are conducted by clinical dermatologists on a daily basis, could be reallocated for level 2 procedures.

None declared.

Ana Carolina Figueiredo Pereira Cherobin: Conception and planning of the study; elaboration and writing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.

Glaysson Tassara Tavares: Approval of the final version of the manuscript; conception and planning of the study; effective participation in research orientation; critical review of the manuscript.

None declared.