Clinical use of topical anesthetics in children

INTRODUCTION — The use of topical anesthetics for pain management during minor procedures in children is reviewed here.

A general approach to the management of pain and sedation in children, and prevention and treatment of neonatal pain are discussed elsewhere. (See "Pain in children: Approach to pain assessment and overview of management principles" and "Management and prevention of pain in neonates".)

MECHANISM OF ACTION — Local anesthetics work by reversibly blocking sodium channels within the nerve fibers, which prevents transmission of pain signals by disrupting depolarization of the nerve (see "Subcutaneous infiltration of local anesthetics", section on 'Anatomy and physiology'). In the skin, these nerve fibers are located in the dermis and epidermis and are covered by the water impermeable stratum corneum. Topical anesthetics overcome this barrier by either passive diffusion from creams or gels or the use of needle-free methods such as pressured gas drug delivery, heat-enhanced diffusion, or iontophoresis [1].

SELECTION OF A TOPICAL AGENT

General principles — Painful procedures, such as venipuncture, intravenous (IV) cannulation, intramuscular (IM) injection, laceration repair, and lumbar puncture (LP) are common in pediatrics and cause distress to children and their caretakers. The stress response to pain is associated with metabolic and hormonal changes that are attenuated by local anesthetics [2,3].

Local anesthetics can be injected; however, topical analgesics, either topical anesthetics or vapocoolant spray can be applied without needles and can reduce the need for physical and chemical restraints [4]. These agents also avoid the tissue distortion that occurs with infiltrated anesthetics [5]. As discussed below, the selection of the topical anesthetic primarily depends upon the type and urgency of the procedure, the provider's knowledge and comfort with different types of application procedures, and patient preference (table 1).

In many children undergoing minimally painful procedures, local anesthetics can be delivered topically to diminish or abolish the pain without the need for sedation, especially when age-appropriate nonpharmacologic interventions are used. When nonpharmacologic interventions and topical anesthetics are not sufficient and minimal sedation is necessary, inhaled nitrous oxide or intranasal midazolam are suggested. (See "Procedural sedation in children: Selection of medications", section on 'Minimally painful procedures'.)

Preparation — Prior to minor painful procedures, nonpharmacologic interventions (eg, behavioral or cognitive techniques) are also essential to attenuate pain in the conscious child and enhance the benefit of local analgesia. A table provides suggested techniques and the appropriate timing of their use prior and during the procedure (table 1). (See "Procedural sedation in children: Approach", section on 'Nonpharmacologic interventions'.)

Immediate-type allergy (including anaphylaxis) to local anesthetics is rare. However local anesthetics can cause contact dermatitis. Avoid topical use in patients with a history of blistering skin lesions or localized eczema after past application. (See "Allergic reactions to local anesthetics".)

Although toxicity is rare and typically associated with excessive application, providers should understand the signs and symptoms of local anesthetic toxicity (eg, seizures and cardiotoxicity) and know the appropriate management. The table provides a rapid overview of this information (table 2).

Selected agents (eg, lidocaine, prilocaine, and benzocaine) also have the potential to cause methemoglobinemia, especially in infants younger than 12 months of age with predisposition to methemoglobinemia (eg, G6PD deficiency or taking methemoglobin-inducing medication), and the provider should be aware of clinical features and treatment of methemoglobinemia as discussed separately. (See "Methemoglobinemia".)

Vascular access or venipuncture — The approach to topical analgesia for vascular access or venipuncture varies for nonurgent or urgent procedures:

●Nonurgent – Whenever available, children should be offered some form of topical analgesia prior to nonurgent venipuncture, IV catheter placement, or percutaneous access of an indwelling central line. We suggest liposomal lidocaine, tetracaine gel, lidocaine-prilocaine cream, a heated lidocaine and tetracaine patch, or needle-free lidocaine administration (eg, J-tip) rather than vapocoolant spray or lidocaine iontophoresis to minimize the pain of venipuncture or vascular access. Needle-free lidocaine administration reduces pain within 1 to 3 minutes of use. For topical agents, minimum application time is 20 to 30 minutes for a heated lidocaine and tetracaine patch, 30 minutes for liposomal lidocaine, 30 to 45 minutes for tetracaine gel, and 60 minutes for lidocaine-prilocaine. The efficacy of all of these agents is roughly equivalent (table 3). The longer application time for lidocaine-prilocaine may practically limit its usefulness relative to the other preparations. Nonpharmacologic approaches are an essential part of optimizing the analgesia for all of these agents (table 1). Needle-free lidocaine delivery is also appropriate to provide analgesia prior to urgent percutaneous vascular access as discussed below.

By contrast, the efficacy of vapocoolant agents is highly dependent upon spraying time [6-8]. Vapocoolant spray application is also uncomfortable, and the duration of analgesia is short and may be inadequate for prolonged attempts at IV access. Lidocaine iontophoresis also provides effective pain relief for venous catheter placement or venipuncture within 10 to 20 minutes [9-12]. However, the discomfort associated with the procedure, the demand on provider time relative to other techniques, significant local skin reactions (including burns), and the emergence of liposomal lidocaine as a nonpainful technique that has an onset of action similar to iontophoresis has limited the use of this technique in clinical practice.

Multiple studies have demonstrated that lidocaine-prilocaine reduces pain associated with procedures such as venous or arterial puncture, placement of IV catheters; access to subcutaneous drug reservoirs, immunization, LP, and laceration repair [1,13,14]. As an example, in a randomized trial in 258 children, subjective pain scores in response to venipuncture and venous cannulation were significantly lower with lidocaine-prilocaine than with placebo [15]. Another randomized trial evaluated the effect of lidocaine-prilocaine on distress and ease of procedure in children undergoing phlebotomy in an office practice [16]. Measures of distress and ease of procedure improved significantly among children who had lidocaine-prilocaine.

Studies that have compared lidocaine-prilocaine to other topical anesthetic formulations, such as liposomal lidocaine, tetracaine gel, or a heated lidocaine and tetracaine patch show that these alternative formulations have equivalent to better pain relief with a shorter onset of action [1,17-24]. First attempt success rate is similar among the cream or gel preparations but is better for the heated patch. As an example, in a multicenter trial of children undergoing IV placement, providers using a heated lidocaine and tetracaine patch had a higher first attempt success rate than those using lidocaine-prilocaine cream (92 versus 85 percent, respectively) [24]. The per-application cost of the gel and cream preparations are similar while the cost of the heated patch is higher.

●Urgent – We suggest that awake patients, who are undergoing urgent venipuncture, IV catheter placement or percutaneous access of an indwelling central line, receive analgesia by needle-free lidocaine delivery or local infiltration of 1% buffered lidocaine solution via a 30-gauge needle rather than administration of vapocoolant spray. Nonpharmacologic techniques appropriate to an urgent procedure should also be used (table 1). (See 'Needle-free lidocaine delivery' below and 'Vapocoolant spray' below and "Subcutaneous infiltration of local anesthetics", section on 'Lidocaine'.)

In stable patients and when equipment and properly trained personnel are available, local analgesia may be augmented by inhalation of nitrous oxide which provides rapid mild to moderate sedation. (See "Pediatric procedural sedation: Pharmacologic agents", section on 'Nitrous oxide'.)

Randomized controlled trials have shown that use of a carbon dioxide propelled needle-free lidocaine delivery reduces the pain of venipuncture or IV insertion within a few minutes of use when compared with placebo and may provide better anesthetic effect than prilocaine-lidocaine, or liposomal lidocaine [25-29]. Although these studies support a rapid reduction of pain by needle-free lidocaine delivery devices relative to placebo, lidocaine-prilocaine, or liposomal lidocaine, the degree of pain relief varies, and the clinical utility of needle-free lidocaine delivery is uncertain for nonemergent procedures. However, the ability to provide analgesia within 1 to 3 minutes of use may make this device helpful for patients undergoing urgent venipuncture or vascular access procedures.

Lidocaine injection and vapocoolant spray are the primary alternatives to needle-free lidocaine delivery when the procedure needs to be accomplished urgently. Onset of action occurs rapidly and analgesia is excellent for injected lidocaine. The pain of injection can be mitigated by using a buffered 1% lidocaine solution and a 30-gauge needle [1]. (See 'Vapocoolant spray' below and "Subcutaneous infiltration of local anesthetics", section on 'Lidocaine'.)

Vapocoolant sprays are uncomfortable to the patient and, due to the brief duration of effect, may require two providers to administer. Analgesia may wear off before the procedure is successfully completed. For all of these reasons, it is an inferior approach to pain control during urgent procedures. (See 'Vapocoolant spray' below.)

Standing orders — In certain jurisdictions, emergency department (ED) standing orders or triage protocols for lidocaine-prilocaine, liposomal lidocaine, or tetracaine gel application in triage permit nurses to place topical anesthetics on children likely to undergo dermal procedures and are utilized in many hospitals (algorithm 1) [30,31]. Standing orders help encourage the use of topical anesthetics and are an important part of implementing a systemic approach to pain management for pediatric venous access in the ED or other hospital unit [32]. Nonpharmacologic approaches should also be used to maximize the benefit of topical anesthetics for pain relief (table 1).

Intramuscular injections — For infants and children undergoing IM injections, we suggest analgesia with topical anesthetics (prilocaine-lidocaine, liposomal lidocaine, or tetracaine gel) prior to injections instead of vapocoolant spray or other cooling methods (eg, application of an ice pack). In a network meta-analysis of eight placebo-controlled trials performed in infants and children undergoing IM injections, lidocaine-prilocaine had a high probability of providing the best pain control when compared with vapocoolant spray or, in neonates and young infants, oral sucrose [33].

Given that studies of other procedures suggest equivalent analgesia among the topical anesthetics, these results suggest that topical anesthetics either alone or, in combination with oral acetaminophen or ibuprofen in older infants and children or, in young infants, oral sucrose may reduce the pain of IM injection to a greater extent than cooling methods. (See 'Lidocaine-prilocaine' below and 'Liposomal lidocaine' below and 'Tetracaine gel' below.)

Other procedures through intact skin — Topical anesthetics may also be used on intact skin for pain management during other procedures such as joint aspiration, paraphimosis reduction, zipper injuries, elective LP, and curettage of molluscum contagiosum as discussed separately:

●(See "Joint aspiration or injection in children: Indications, technique, and complications", section on 'Anesthesia'.)

●(See "Paraphimosis: Clinical manifestations, diagnosis, and treatment", section on 'Pain control'.)

●(See "Management of zipper entrapment injuries", section on 'Local anesthesia'.)

●(See "Lumbar puncture in children", section on 'Procedure'.)

●(See "Molluscum contagiosum", section on 'Curettage'.)

Laceration repair — For uncomplicated facial or scalp lacerations <5 cm in length, we suggest initial pain control with topical LET (lidocaine-epinephrine-tetracaine) rather than injected local anesthetic. In addition, LET may reduce the pain of local infiltration of anesthetics for lacerations on other parts of the body with the exception of sites near mucus membranes, poorly vascularized sites (eg, auricle), or genitalia where placement of LET is contraindicated. However, it does not typically provide complete analgesia [34]. LET is available in an aqueous solution and a methylcellulose based gel. The gel is preferred because it maintains better contact with the open wound and is easier to apply. (See 'Lidocaine-epinephrine-tetracaine (LET)' below.)

A maximum of 3 mL of LET gel or solution should be applied for at least 20 minutes prior to laceration repair. Irrigation of the wound and removal of debris and blood clots before application maximizes penetration of the anesthetic although it is not necessary for most simple lacerations [35]. LET dosing, application, and adverse effects are discussed in greater detail below. (See 'Lidocaine-epinephrine-tetracaine (LET)' below.)

LET should not be applied to mucosal surfaces or in areas that have an end arterial supply, such as the tips of digits, penis, nose, and ears [17,34]. LET is not recommended for large wounds (>5 cm in length) or multiple lacerations with a total length of >5 cm because the amount required for adequate anesthesia might exceed the recommended dose and risk toxicity [17,34,36].

LET is the topical anesthetic most frequently used for laceration repair. Based upon several trials, it provides adequate local anesthesia for wound closure in 75 to 90 percent of scalp and facial lacerations [34,36-38]. If anesthesia is inadequate with LET alone, supplemental 1% lidocaine solution without epinephrine and, buffered, when available, is injected through the wound edges for suturing. LET also reduces the pain of lidocaine injection [39,40]. (See 'Lidocaine-epinephrine-tetracaine (LET)' below and "Subcutaneous infiltration of local anesthetics", section on 'Lidocaine'.)

Depending upon the patient and the specific type of wound closure, mild or deeper sedation may also be required for optimal laceration closure. (See "Procedural sedation in children: Selection of medications", section on 'Approach'.)

Standing orders — In order to expedite care and where permitted, many hospital EDs have standing orders or triage protocols for application of LET to lacerations in triage [30]. When implementing standing orders, we suggest the following criteria [30]:

●Eligible patients – Simple lacerations <5 cm in length (age >3 months and weight >5 kg)

●Contraindications

•Lacerations of mucous membranes (eg, lip, vulva) or regions where it may cause vascular compromise (eg, digits, penis, ear, nose)

•Grossly contaminated wounds

•Patients with allergy to amide or ester local anesthetics

●Procedure

•Place 3 mL of LET mixed with cellulose on the open wound (preferred) OR apply LET solution into the wound as described separately (see 'Lidocaine-epinephrine-tetracaine (LET)' below)

•Cover with an occlusive dressing (eg, gauze with tape or adhesive polyurethane film dressing [eg, Tegaderm or Opsite]) for at least 30 minutes

•Document the time of placement in the patient's medical record

Mucosal surfaces — When properly used, topical anesthetic mucosal preparations (eg, lidocaine, lidocaine-prilocaine, benzocaine, xylocaine, and amethocaine) have been shown to decrease the pain of intraoral dental injections [41-43]. Lidocaine preparations are equivalent or superior to benzocaine. Benzocaine use is not recommended in children because of the risk of toxicity. (See 'Viscous lidocaine' below and 'Benzocaine' below.)

Although evidence is lacking regarding the use of topical anesthetics in children undergoing nasopharyngoscopy, trials in adults indicate, at most, a small reduction in pain over vasoconstrictor medication and lubricants [44]. By contrast, topical anesthetics significantly reduce pain and gagging during nasogastric tube placement in adults and, when used with close attention to dose, may be beneficial in children undergoing this procedure [45-47].

Evidence does not support the routine use of topical anesthetics (eg, viscous lidocaine) during minor procedures involving the urethra or the oropharynx in children because of limited efficacy and the potential risk of local anesthetic toxicity or methemoglobinemia. For example, viscous lidocaine does not significantly reduce the pain of urethral catheterization in infants compared with lubricant alone [48,49]. Viscous lidocaine also has limited impact on reducing the pain of intraoral lesions caused by herpetic gingivostomatitis when compared with placebo gel which may be a proxy for its efficacy for pain control during repair of intraoral lacerations [50]. (See "Urine collection techniques in infants and children with suspected urinary tract infection", section on 'Transurethral bladder catheterization' and "Herpetic gingivostomatitis in young children", section on '"Magic mouthwash" and other topical therapies'.)

The use of topical anesthetics for awake intubation is discussed separately. (See "Clinical use of local anesthetics in anesthesia", section on 'Topical anesthetics'.)

Use in neonates — The use of topical anesthetics for pain control in neonates is discussed separately. (See "Management and prevention of pain in neonates", section on 'Topical anesthetics'.)

AGENTS FOR INTACT SKIN

Lidocaine-prilocaine — Lidocaine-prilocaine (eg, EMLA [an acronym for "eutectic mixture of local anesthetics"], Oraqix, Lidopril, Priloxx) consists of 2.5%lidocaine and 2.5% prilocaine in a cream base. A eutectic mixture has a lower melting point than its individual components; consequently, it is in liquid form at room temperature [51,52]. The anesthetics in lidocaine-prilocaine cream are concentrated in micron-sized droplets. The small size of the droplets and the high concentration gradient promote penetration of the anesthetic through intact skin [51,53].

●Dose – Typical dosing for venipuncture is as follows: Apply 1 to 2 g of lidocaine-prilocaine cream per 10 cm² of skin in infants and children three months of age or older and who weigh at least 5 kg. Lidocaine-prilocaine is supplied as a 5 g or 30 g tube. Estimation of dose is easier with the smaller tube. Typical application involves placing lidocaine-prilocaine on two sites prior to the procedure; the preferred site and a back-up site in case the first attempt is unsuccessful.

The cream should be covered with an occlusive dressing (eg, gauze with tape or adhesive polyurethane film dressing [eg, Tegaderm or Opsite]) for 45 to 60 minutes.

Lidocaine-prilocaine cream requires approximately one hour to achieve peak effect. In one study, the depth of anesthesia measured by needle insertion was approximately 3 mm one hour after application to intact skin; maximum penetration was 5 mm after 1.5 to 2 hours. The depth of anesthesia penetration continued to increase for 30 to 60 minutes after removal of the cream. Lidocaine-prilocaine effectively reduces pain for at least 1 to 2 hours after removal of the cream. The duration of action can last as long as four hours [2,51,54].

●Precautions and adverse effects – Contraindications to the use of prilocaine-lidocaine include conditions requiring rapid treatment, known sensitivity to lidocaine, prilocaine, or other amide type anesthetics; congenital or idiopathic methemoglobinemia, and, in infants 12 months of age and younger, predisposition to methemoglobinemia such as glucose-6-phosphate dehydrogenase deficiency or concurrent use of methemoglobin-inducing medications (table 4) [17,55].

Adverse reactions associated with lidocaine-prilocaine cream include mild, transient skin irritation and methemoglobinemia attributable to the prilocaine in the formulation [17,56]. With appropriate application, plasma concentrations of the anesthetics are low, and the increase in methemoglobin level is negligible [17,56]. However, cases of methemoglobinemia, seizures, and respiratory depression have been described with excessive skin application in children, including those patients with skin conditions that may have increased systemic absorption, such as atopic dermatitis [56-58]. Methemoglobinemia is also more likely to occur in infants younger than three months of age and in children with a predisposing condition, such as glucose-6-phosphate dehydrogenase deficiency or concurrent use of methemoglobin-inducing medications (table 4) [17,56,58]. (See "Methemoglobinemia".)

Contact dermatitis may rarely occur following lidocaine-prilocaine application [59].

Liposomal lidocaine — Liposomal lidocaine (eg, LMX [formerly known as ELA-Max]) consists of topical preparation of lidocaine encapsulated in liposomes. LMX may be followed by a numeral, such as LMX 4 or LMX 5, which indicates the percent strength of lidocaine in the preparation. Liposomes facilitate the rate and extent of drug absorption and protect the drug from being rapidly metabolized [18]. This product is available without a prescription. In contrast to lidocaine-prilocaine, application of liposomal lidocaine does not require an occlusive dressing and the recommended duration of treatment is 30 rather than 60 minutes.

●Dose – When used for intravenous (IV) access or venipuncture, 1 to 2.5 g of LMX-4 cream (4% lidocaine) can be applied to 6.25 cm² of skin in infants and children older than one month of age [60,61]. Liposomal lidocaine is supplied as a 5 g, 15 g, and 30 g tube. Estimation of dose is easier with the smaller tube. Typical application involves placing lidocaine-prilocaine on two sites prior to the procedure; the preferred site and a back-up site in case the first attempt is unsuccessful.

LMX-4 should be applied 30 minutes before the procedure. The area does not need to be covered for effective analgesia; however, active children could disrupt the cream and covering the area with a polyurethane dressing (eg, Tegaderm or Opsite) may be protective.

●Precautions and adverse effects – As described above for lidocaine-prilocaine, liposomal lidocaine should not be used in patients with lidocaine or amide anesthetic allergy. Lidocaine toxicity (arrhythmias, seizures, coma, and death) may occur if liposomal lidocaine is applied to large areas of the skin for prolonged periods of time or applied to broken skin, rashes, or areas of skin irritation. Thus, clinicians should ensure that liposomal lidocaine is applied to limited areas of intact skin for the proper amount of time. (See 'Lidocaine-prilocaine' above.)

No serious adverse events have been described with routine use of liposomal lidocaine [18]. In addition, no clinically significant systemic absorption of lidocaine was apparent among 10 children, 3 to 15 years of age, when serum lidocaine concentrations were measured after a 60-minute application. Safety data is lacking for infants and children younger than two years of age. (See "Methemoglobinemia" and "Subcutaneous infiltration of local anesthetics", section on 'Lidocaine'.)

Tetracaine gel — Tetracaine gel (eg, Ametop) contains 40 mg of tetracaine per 1 g of gel (4 percent weight/weight) and is widely used outside of the United States.

●Dose – Apply 1 g per 6.25 cm² of skin and cover with an occlusive dressing (eg, gauze with tape or adhesive polyurethane film dressing [eg, Tegaderm or Opsite]) for 30 to 45 minutes [21]. Tetracaine gel is supplied as a 1.5 g tube that delivers 1 g of drug when squeezed.

Duration of action approaches four to six hours. Skin erythema is a normal consequence of tetracaine-induced capillary dilation and may assist in venous cannulation.

●Contraindications and precautions – Tetracaine gel should not be used in premature infants, full term infants under one month of age, and patients with ester anesthetic allergy. Cardiac arrhythmias, including wide complex tachycardia and reversible hemodynamic instability, have been reported when tetracaine was applied to the antecubital fossa for an IV access procedure in a two day old premature infant [62].

Self-heating lidocaine and tetracaine topical patch — The self-heating lidocaine and tetracaine patch (Synera, Pliaglis) contains 70 mg lidocaine and 70 mg tetracaine [1].

●Dose – Apply one patch to intact skin for 20 to 30 minutes and promptly remove. After one failed attempt, one additional patch may be applied in children [63]. Simultaneous application of more than one patch is not recommended in children. The top cover of the patch should not be cut or removed because this action may lead to burn injury.

●Precautions and adverse effects – The patch should not be used in patients with sensitivity to amide or ester local anesthetics or para-aminobenzoic acid hypersensitivity [63]. The heating element contains iron. Thus, the patch must be removed before some diagnostic procedures, especially magnetic resonance imaging.

Prolonged application of the patch to intact skin or application to broken skin or mucous membranes may result in serious local anesthetic toxicity including seizures, cardiac arrhythmias, and methemoglobinemia [63].

Approximately 90 percent of the drug content remains in the patch after use.

With routine use, redness and local swelling of the skin at the application site may occur but should rapidly resolve after the patch is removed.

Needle-free lidocaine delivery — Another method of lidocaine delivery uses compressed gas to deliver a liquid form of lidocaine (J-Tip Needleless Injection System).

●Dose – This device administers 2 to 2.5 mg (0.2 to 0.25 mL of a buffered 1% lidocaine solution) utilizing a carbon dioxide cartridge [1]. The device is supplied separately from the drug and is filled by a pharmacist and stored at room temperature or filled at the bedside by the provider just prior to administration. The manufacturer suggests the use of 1% buffered lidocaine or preservative-free lidocaine without epinephrine to minimize any burning or stinging. The clinician should consult the device manufacturer's instructions for details on usage [64]. The provider should ensure that the device is not applied directly over a vein during administration. Analgesia is typically achieved within 1 to 3 minutes.

The pain of administration with a this device is low [25,27,28], and its use does not impact first-attempt success rate [65]. The system produces an audible "pop" when deployed that may cause additional anxiety in the patient [27]. In one trial of 197 children, carbon dioxide-propelled lidocaine was no more effective than carbon dioxide-propelled isotonic saline for managing the pain of needle insertion suggesting that the analgesia achieved within 1 to 2 minutes may derive more from the physical effects of subcutaneous fluid injection rather than direct effects of the drug [29].

The cost of a single device relative to a single application of lidocaine-prilocaine or liposomal lidocaine is comparable.

●Precautions and adverse effects – Patients with a known allergy to lidocaine or other amide anesthetics should not receive lidocaine analgesia.

Elevated serum lidocaine levels have been described in patients undergoing analgesia with the J-tip system for peripheral IV access [66]. However, serious lidocaine toxicity, although theoretical possible, has not been reported.

Vapocoolant spray — These agents act by surface cooling of the skin immediately prior to venipuncture, IV placement, or intramuscular (IM) shot [1]. Local cooling may desensitize skin pain receptors and/or inhibit spinal cord pain signals by a specific cold temperature nerve impulse.

Ethyl chloride, a flammable anesthetic, is the most studied vapocoolant spray. It is also combined with dichlorotetrafluoroethane in a prescription freezing spray (eg, Fluro-Ethyl) [1]. Other products (Pain Ease, Instant Ice) utilize 1,1,1,3,3,-pentafluoropropane and 1,1,1,2,-tetrafluoroethane in spray form which is not flammable or ozone depleting. Ethyl chloride should be used on intact skin and may be used in patients with cellulitis or other lesions. 1,1,1,3,3,-pentafluoropropane with 1,1,1,2,-tetrafluoroethane (eg, Pain Ease, Instant Ice) is designed for use on intact skin, minor open wounds, and intact mucous membranes.

●Dose – The goal is to spray long enough to cause skin blanching without freezing. Spraying should cease as soon as the skin blanches to avoid frostbite.

For ethyl chloride liquid, application is generally three to seven seconds [67]. For mist sprays, application is up to 10 seconds. The distance from the skin surface should be 3 to 9 inches during administration. Once blanching is achieved, analgesia lasts approximately 60 seconds.

●Precautions and contraindications – Ethyl chloride should not be used near open flames or electrocautery [68].

Vapocoolant sprays are not recommended in diabetics or patients with poor circulation or insensitive skin. Vapocoolant sprays should not be administered to patients with allergies to spray components (eg, ethyl chloride, 1,1,1,3,3,-pentafluoropropane, or 1,1,1,2,-tetrafluoroethane) [68]. Care should be taken to avoid eye contact during vapocoolant spray application because of potential for chemical irritation.

Freezing may alter skin pigmentation [1].

Inhalation of products that contain ethyl chloride may produce narcotic and general anesthetic effects including coma with depression of respiration and cardiac activity.

Lidocaine iontophoresis — Iontophoresis uses an electric current from two externally placed electrodes to move ionized lidocaine across the stratum corneum barrier to the dermis, where it blocks nerve endings [9]. The rate of anesthetic transport is higher with iontophoresis than passive diffusion [10,11,34].

●Dose – Lidocaine is administered in a volume of 0.6 to 1.0 mL of 2% lidocaine with epinephrine. The electric current delivered is titrated from 0 to a maximum of 4 milliamperes (mA). A current of 0.2 mA/cm² applied for 10 minutes achieves an anesthetic depth of 5 to 7 mm [69]. Delivery of the drug is proportional to the product of the electric current and the application time [10].

The onset of anesthesia occurs approximately 10 to 20 minutes after administration begins [34]. The duration is approximately 30 minutes.

●Precautions and adverse effects – Lidocaine iontophoresis should not be used in patients with sensitivity to lidocaine or other amide anesthetics or with lesions near the eye [10,34]. In addition, it should not be used over metal indwelling catheters or in patients with pacemakers.

Adverse effects of iontophoresis are limited to local skin reactions, such as transient erythema, urticaria, blisters, and superficial burns [10,11]. Tingling, burning, and/or itching sensations may occur under the electrodes. Lidocaine toxicity has not been reported.

AGENTS FOR LACERATION REPAIR

Lidocaine-epinephrine-tetracaine (LET) — LET is a combination of lidocaine (4%), epinephrine (0.1%), and tetracaine (0.5%) available as an aqueous solution or methylcellulose-based gel. The dose, application, and adverse effects are as follows:

●Dose and application – LET in a dose of 1 to 3 mL is applied to an open wound for 20 to 30 minutes. The method of application depends upon whether gel or solution is being applied:

•Gel – Gels are applied to the wound and wound edges with a cotton-tipped applicator [36,38]. The wound is then covered with sterile gauze held in place by an adhesive dressing, tape, or an elastic wrap for 20 to 30 minutes. The gel is removed before suturing. The duration of action following removal of the anesthetic is 45 to 60 minutes [34].

Gels provide similar anesthesia to aqueous solutions but offer practical advantages. In one study of suturing of uncomplicated scalp and facial lacerations in 200 children, more patients treated with gel had complete anesthesia (85 versus 76 percent) and fewer had partial anesthesia (5 versus 21 percent), although more had incomplete anesthesia (9 versus 3 percent), compared with the solution [38]. In addition, problems seen with the solution, such as difficulty in application, loss of anesthetic volume due to drainage from the laceration, and inadvertent contact with mucous membranes, are less likely with the gel.

•Solution – The aqueous solution of LET is first painted into the wound with a cotton-tipped swab. This application is then be repeated every 3 to 5 minutes [37,38]. Anesthesia becomes effective in approximately 20 to 30 minutes.

Alternatively, a saturated cotton ball can be applied directly to the laceration after initial application and held in place with tape although experience suggests that this method may not be as effective, especially for deep or oozing wounds.

The clinician should ensure that the solution does not come in contact with mucous membranes.

The use of up to 3 mL of LET gel or solution as described is supported by extensive clinical experience with this dose without reported serious adverse effects. As an example, in a trial of 203 children between the ages of three months to 17 years receiving 3 mL of LET prior to wound closure with tissue adhesives, no serious toxicity occurred in any patient [70]. Although the administered dose of lidocaine in 3 mL of LET is approximately 135 mg, the amount of lidocaine and tetracaine actually absorbed is limited by the size of the laceration and the presence of epinephrine. Much larger topical doses of lidocaine without epinephrine (up to 90 mg/kg) have been tolerated in adults with partial thickness burns without serious toxicity although the plasma concentration of lidocaine (5.8 mcg/mL) was above the therapeutic level [71].

Weight-based dosing has been suggested for children <17 kg (eg, 0.175 mL/kg) to prevent application of >5 mg/kg of lidocaine [31]. This approach appears conservative given the lack of toxicity associated with the use of LET; evidence is lacking to indicate that weight-based dosing is needed.

Alternatively, clinicians can use dosing guidance as for other local anesthetic formulations. However, LET is likely to have lower potential for systemic absorption than these agents due to epinephrine-induced vasoconstriction. (See 'Liposomal lidocaine' above.)

●Precautions and adverse effects – Contraindications to the use of LET include allergy to amide or ester topical anesthetics. Because of the higher potential for systemic absorption of topical agents in neonates and the theoretical risk of methemoglobinemia posed by the tetracaine component, LET should be used with caution in infants younger than one month of age.

Adverse effects arise from excessive absorption of lidocaine-tetracaine, resulting in systemic toxicity often after mucous membrane exposure or ingestion of a large dose. Adverse effects are rare if recommended doses are not exceeded and application to mucous membranes is avoided [36]. For example, a systematic review of 23 randomized controlled trials in 3218 patients that assessed multiple topical anesthetics, including LET, found no reports of serious complications [72].

Toxicity of lidocaine and tetracaine include central nervous system (CNS) symptoms manifests with headache, irritability, restlessness, metallic taste, tingling around the lips, somnolence, blurred vision, and seizures. Cardiovascular toxicity consist of bradycardia, decreased contractility, atrioventricular block, vasodilation, ventricular ectopy, and cardiac arrest [73]. (See "Local anesthetic systemic toxicity", section on 'Clinical presentation of toxicity'.)

Methemoglobinemia has rarely been reported in association with the use of topical lidocaine. (See "Methemoglobinemia", section on 'Acquired methemoglobinemia'.)

Tetracaine-adrenaline-cocaine (TAC) — TAC is a combination of tetracaine (0.25 to 0.5%), adrenaline (epinephrine, 0.025 to 0.05 percent), and cocaine (4 to 11.8 percent). It is available as a solution or gel. Tetracaine and cocaine provide topical anesthesia [35,37]. Cocaine and adrenaline cause local vasoconstriction that limits systemic absorption and minimizes bleeding.

TAC was among the first topical anesthetics developed. It is comparable to lidocaine infiltration in providing anesthesia for scalp and facial lacerations, and has been widely used for laceration repair in pediatric patients [35,72,74].

TAC is safe if used correctly. However, misapplication or mucous membrane exposure may result in serious systemic toxicity such as hyperexcitability, seizures, stroke, cerebral hemorrhage, tachycardia, arrhythmias, malignant hypertension, and cardiac arrest [5,17,36]. In addition, cocaine is a controlled substance with the potential for misuse. Its cost far exceeds that of lidocaine [37,72]. As a result, TAC has largely been replaced by other topical anesthetics with similar efficacy, primarily LET [5,13,37,38].

AGENTS FOR MUCOSAL SURFACES

Viscous lidocaine — Viscous lidocaine, available as in a 2% concentration (20 mg/mL), is the most commonly used mucosal anesthetic preparation in children.

●Dose – For application to mucosal surfaces, do not exceed 4 mg/kg (0.2 mL/kg of the 2% [20 mg/mL] concentration).

●Precautions and adverse effects – Viscous lidocaine should not be used in patients with lidocaine or amide anesthetic allergy.

As with other lidocaine-containing preparations, lidocaine toxicity (arrhythmias, seizures, coma, and death) and, rarely, methemoglobinemia may occur if an excessive dose of viscous lidocaine is administered [75].

Benzocaine — Benzocaine-containing sprays or gels should be avoided in children [76]. Alternative agents, such as lidocaine spray or 2% viscous lidocaine are much less likely to cause methemoglobinemia and appear to have similar efficacy. (See "Methemoglobinemia", section on 'Topical anesthetics'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Topical anesthetics in children".)

SUMMARY AND RECOMMENDATIONS

●General principles – Topical analgesics, either topical anesthetics or vapocoolant spray, can be applied without needles and can reduce the need for physical restraint or sedation for minor procedures. They also avoid the tissue distortion that occurs with infiltrated anesthetics. (See 'Selection of a topical agent' above and 'General principles' above.)

Prior to minor painful procedures, nonpharmacologic interventions (eg, behavioral techniques, cognitive techniques (table 1)) are essential adjuncts to topical analgesia. They help attenuate pain in the conscious child and enhance the benefit of local analgesia. (See "Procedural sedation in children: Approach", section on 'Nonpharmacologic interventions'.)

●Preparation – Before applying topical anesthetics, the provider should ensure that the patient has no known allergy to lidocaine, tetracaine, or other amide- or ester-type anesthetics. Although toxicity is rare and typically associated with excessive application, providers should understand the signs and symptoms of local anesthetic toxicity and know the appropriate management. The table provides signs and symptoms and recommended management of seizures and cardiotoxicity in patients with systemic toxicity from local anesthetics (table 2). (See 'Preparation' above.)

Selected agents (eg, lidocaine, prilocaine, and benzocaine) also have the potential to cause methemoglobinemia, and the provider should be aware of clinical features and treatment of methemoglobinemia. (See "Methemoglobinemia".)

●Topical anesthesia by indication – Topical anesthesia is effect for a variety of procedures:

•Vascular access or venipuncture – The approach to topical analgesia for vascular access or venipuncture varies for nonurgent or urgent procedures (see 'Vascular access or venipuncture' above):

-Whenever available, children should be offered some form of topical analgesia prior to nonurgent venipuncture, intravenous (IV) catheter placement, or percutaneous access of an indwelling central line. For these patients, we suggest liposomal lidocaine, tetracaine gel, lidocaine-prilocaine cream, a heated lidocaine and tetracaine patch (table 3), or needle-free lidocaine administration rather than vapocoolant spray or lidocaine iontophoresis (Grade 2B).

-For awake patients who are undergoing urgent venipuncture, IV catheter placement or percutaneous access of an indwelling central line, we suggest analgesia by needle-free lidocaine delivery or local infiltration of 1% buffered lidocaine solution via a 30-gauge needle, depending upon patient and caregiver preference, rather than administration of vapocoolant spray (Grade 2C).

•IM injections – For infants and children undergoing nonurgent intramuscular (IM) injections, we suggest analgesia with topical anesthetics (prilocaine-lidocaine, liposomal lidocaine, or tetracaine gel) rather than vapocoolant spray or other cooling methods (eg, application of an ice pack) prior to IM injections (Grade 2C). (See 'Intramuscular injections' above.)

•Laceration repair – For patients with uncomplicated facial or scalp lacerations <5 cm in length, we suggest initial pain control with topical LET (lidocaine-epinephrine-tetracaine) rather than injected local anesthetic (Grade 2C). (See 'Laceration repair' above and 'Lidocaine-epinephrine-tetracaine (LET)' above.)

LET is available in an aqueous solution and a methylcellulose based gel. The gel is preferred because it maintains better contact with the open wound and is easier to apply. In addition, LET may reduce the pain of local infiltration of anesthetics for lacerations on other parts of the body with the exception of sites near mucus membranes, poorly vascularized sites (eg, auricle), or genitalia where placement of LET is contraindicated. However, it does not typically provide complete analgesia. (See 'Lidocaine-epinephrine-tetracaine (LET)' above.)

•Dental and nasopharyngeal procedures – Application of topical anesthetics to mucosal surfaces reduces the pain of intraoral dental injections and may be helpful for nasopharyngeal procedures, such as nasopharyngoscopy and nasogastric tube placement. In children, evidence does not support the routine use of topical anesthetics (eg, viscous lidocaine) during minor procedures involving the urethra or the oropharynx because of limited efficacy and the potential risk of local anesthetic toxicity or methemoglobinemia. (See 'Mucosal surfaces' above.)

●Options for minimal sedation – In many children undergoing minimally painful procedures, local anesthetics can be delivered topically to diminish or abolish the pain without the need for sedation, especially when age-appropriate nonpharmacologic interventions are used. When nonpharmacologic interventions and topical anesthetics are not sufficient and minimal sedation is necessary, inhaled nitrous oxide or intranasal midazolam are suggested. (See "Procedural sedation in children: Selection of medications", section on 'Minimally painful procedures'.)

●Standing orders – Emergency department (ED) standing orders in triage permit nurses to place topical anesthetics on children likely to undergo dermal procedures or laceration repair and are utilized in many hospitals (algorithm 1). (See 'Standing orders' above and 'Standing orders' above.)