Topical Anesthetics and Tissue Adhesives: A New Generation in Pediatric Wound
Topical Anesthetics and Tissue Adhesives: A New Generation in Pediatric Wound Management
Authors: Laura Sells, MD, Fellow, Section of Emergency Medicine, Department of Pediatrics, Ohio State University Children’s Hospital, Columbus, OH; Leslie Mihalov, MD, Chief, Section of Emergency Medicine, Department of Pediatrics, Ohio State University Children’s Hospital, Columbus, OH.
Peer Reviewer: Richard M. Ruddy, MD, Director, Emergency Medicine, Children’s Hospital Medical Center; Professor of Clinical Pediatrics, University of Cincinnati College of Medicine.
The evaluation and management of minor injuries and lacerations is a routine part of the daily work of emergency physicians and office-based practitioners. More than 12 million patients are evaluated each year for minor laceration repair.1 Children represent a significant number of these visits. One-third of all injuries in children involve a laceration, making minor wound care an important skill for pediatric care providers.2 A significant amount of research in the area of wound management has been conducted in the last few years as new products and techniques are developed for patient care. New attention is being focused on pediatric pain management as well as on patient costs and efficient use of medical resources. The introduction of topical anesthetic agents and tissue adhesives for laceration repair is changing the face of pediatric wound management, and these products promise to have an even greater role in future medical practice. It is important for all pediatric care providers to become familiar with the products available for wound repair, their indications for use, and their limitations in practice.
— The Editor
Local Anesthetics
Local anesthetic agents are among the most commonly used medications in the emergency department. Significant research has been devoted to developing agents which are effective in producing analgesia while limiting toxicity, pain, and cost. Cocaine was the first local anesthetic described in medical practice. In the late 1800s, it was reported cocaine could be used topically to produce analgesia in the eye.3 Cocaine is a benzoic acid ester and is related to the class of ester anesthetics which includes benzocaine, tetracaine, and procaine. In the 1940s, lidocaine was introduced as the first amide-linked anesthetic. Other amide anesthetics include bupivacaine, mepivacaine, and etidocaine. Whereas the ester-linked anesthetics undergo metabolism by the pseudocholinesterase system, amide compounds undergo hepatic degradation.4-6
Infiltrative Agents
Lidocaine is the most widely used local anesthetic agent. It is readily available, effective, inexpensive, and produces minimal toxicity. It blocks the conduction of action potentials in nerve fibers by inhibiting ion flux through sodium channels.7 The dose of lidocaine for infiltration of a wound may be used up to 4.5 mg/kg. When epinephrine is added, the maximum dose is 7.0 mg/kg.8 It reaches its peak analgesic action approximately five minutes after injection. Analgesia can last as long as two hours, however, most practitioners find its clinical efficacy to be much shorter. Lidocaine, without epinephrine added, can be used for wounds in any area of the body and has particular benefit in that it can be used for lacerations on or near mucosal surfaces.
Most toxicity associated with lidocaine use is related to repeated local injections and misuse of viscous compounds. Toxic effects occur in progression from central nervous system involvement to cardiovascular manifestations. Symptoms including irritability, anxiety, paresthesias, seizures, and coma have all been described. Significant overdose can lead to ventricular fibrillation or even cardiac arrest.7,9 True allergy to lidocaine is uncommon. The methylparaben additive used as a preservative is thought to be the most common cause of allergic reaction.10 This additive is sometimes found in ester anesthetics as well. For those patients with a history of significant adverse reaction to lidocaine, substituting an ester for an amide compound may not be sufficient.
One of the greatest adverse effects with lidocaine is the pain associated with infiltration. Pain with injection is due in part to the acidic nature of the compound. Lidocaine is actually a weak base with a pH of 7.9. It is marketed with the addition of the methylparaben preservative to increase its shelf-life. This preservative decreases the pH of lidocaine into the acidic range (pH 5-7). Studies have shown that buffering lidocaine does decrease the pain associated with injection.11 Buffering with sodium bicarbonate (1 mL NaHCO3 to 9 mL lidocaine) changes the drug to its uncharged state. It is the uncharged form of the molecule that crosses cell membranes and acts within the nerve cells. Although pH has a role in the pain associated with infiltration, studies have documented that other acidic compounds used as anesthetics are not as painful on injection as lidocaine. The pain associated with injection appears to be related primarily to the speed at which the molecules diffuse into the nerve cells, not specifically a function of the pH.
A final complication with the use of lidocaine and other infiltrated anesthetics is that they have the tendency to distort the margins of a laceration. With facial lacerations in particular, it is important to have a well-approximated, precise closure. When wound margins are distorted by infiltration of lidocaine, there is an increased likelihood of adversely affecting the final cosmetic outcome. In children who may not be cooperative with laceration repair to begin with, this is an important additional consideration when preparing for wound closure.
The addition of vasoconstrictors to anesthetic agents is important to their function. Vasoconstrictors such as epinephrine increase the duration and potency of analgesia when combined with anesthetics.4,6 Most local anesthetics are mild vasodilators. Vasoconstriction at the site of infiltration allows more anesthetic to remain at the wound and not be removed by local blood flow. Systemic absorption of anesthetic agents is limited by the addition of vasoconstrictors, so the maximum dose of anesthetic which can be used in a wound is increased. Although they potentiate the effects of anesthetics, the use of vasoconstrictors does limit the clinical application of these drugs. Vasoconstrictors are contraindicated in digits, on the nasal alae, penis, and pinna. These are areas perfused by end-arteriolar blood supply and are subject to tissue ischemia if blood flow is compromised by vasoconstriction.
There are few alternatives to the use of amide or ester anesthetics for infiltrative analgesia.
Wilson and colleagues recently studied the anesthetic effect of benzyl alcohol with epinephrine.12 Benzyl alcohol is an opium alkaloid with anesthetic properties. It is used as an antiseptic agent in many products because of its bacteriostatic action. It is commonly added to saline solution (0.9% benzyl-alcohol bacteriostatic saline solution). Benzyl alcohol has been studied for potential toxicity and has been determined to be relatively non-toxic even in large doses. When combined with epinephrine, it is reported to be less painful on injection than buffered lidocaine or placebo. Benzyl alcohol does appear to provide adequate anesthesia for simple procedures; however, its duration of action is much shorter than that of lidocaine. In an earlier study, Lugo-Janer and associates reported that intradermal infiltration provided effective anesthesia for simple surgical procedures such as shave excisions and curettage.13 When used subcutaneously for wound repair, the duration of anesthesia was shorter and the volume of agent required was more than with lidocaine. Despite its shortcomings, there may be a future role for benzyl alcohol in wound management. It could be effective for those patients with an allergy to lidocaine or other anesthetics. It could also be used in areas where topical anesthetics are contraindicated or non-efficacious. Benzyl alcohol may offer analgesia of long enough duration to accomplish wound irrigation and debridement in conjunction with closure of a wound using tissue adhesive.
Diphenhydramine has also been studied for its anesthetic properties.14,15 Most local anesthetics have antihistamine properties and the H1 antagonists all have some function as local anesthetics. Diphenhydramine has been used extensively as a local anesthetic in dental, urologic, and GI procedures. When used for wound repair, Ernst and colleagues reported that diphenhydramine was actually more painful on injection than lidocaine. Furthermore, the quality of analgesia produced was not as great as with lidocaine. The reported side effects with the use of diphenhydramine are a final consideration. Systemic effects, including sleepiness and dizziness, may occur and significant local reactions have been documented. For these reasons the manufacturers of diphenhydramine currently recommend that it should not be used a local anesthetic agent for laceration repair.
Topical Agents
The introduction of topical anesthetic agents is an important advance in pain management for wound repair. Topical agents are easy to apply, painless, and do not distort wound margins, unlike infiltrated drugs. Children who present for laceration repair are often frightened and uncooperative with caregivers. Topical agents can decrease the need for painful infiltration, which can further reduce the need for sedation and physical restraint. Improved patient cooperation will increase the likelihood of successful wound closure and lessen the psychological trauma associated with laceration repair.
Topical anesthetic agents have been used in medical subspecialties for many years. Their greatest role has been with mucosal application for invasive procedures. Topical anesthetic use for laceration repair has been limited but has increased tremendously in the last decade. Topical agents are ideally suited for small wounds that are less than 4-6 cm in length. They work most effectively on the face and scalp, which are areas of high vascularity. It is felt that these areas are most responsive to topical application because the increased vascularity allows for greater diffusion of anesthetic agent and, therefore, a wider margin of analgesia. Furthermore, because of the accuracy desired in closure of facial and scalp lacerations, repair may begin nearer to the wound margins where the anesthetic activity is the greatest.16 When applied correctly, topical agents are very effective in providing a high degree of anesthesia for wound repair. (See Table 1.)
| Table 1. Commonly Used Medications | |||||
| COMPOUND | DOSE | ONSET | DURATION | COST* | LIMITATIONS |
| Lidocaine 1% | Maximum 4.5 mg/kg | 2-5 minutes | 1-2 hours | $1.29 | Pain |
| 5-mL bottle | Maximum dose in children | ||||
| Lidocaine 1% | Maximum 7.0 mg/kg | 2-5 minutes | 1-2 hours | $1.23 Pain | |
| with Epinephrine | 10 mL bottle | Not for use in areas of end-arteriolar supply | |||
| TAC Solution | 1mL /10 kg body weight | 10-30 minutes | ~1 hour | $16.39 | Risk of systemic toxicity |
| (Tetracaine 0.5%, | Maximum 100 mg | 3-mL syringe | Cost | ||
| Adrenaline 1:2,000, | topically | Schedule II drug | |||
| Cocaine 11.8%) | Not for mucous membranes | ||||
| or end arteriolar supply | |||||
| Best for face, scalp | |||||
| Inadequate for trunk, extremities | |||||
| Shelf life of 3 months, refrigerated | |||||
| LET Gel | Maximum 3 mL | 20-30 minutes | ~1 hour | $1.32 | Slower onset than infiltration |
| (Lidocaine 4%, | 3-mL syringe | Not for mucous membranes | |||
| Epinephrine 0.1%, | or end-arteriolar supply | ||||
| Tetracaine 0.5%) | Best for face, scalp | ||||
| Inadequate for trunk, extremities | |||||
| Shelf life of 5 months, refrigerated | |||||
| EMLA | ~2.5 gm/site | 60 minutes | ~2 hours | $4.87 | Slow onset |
| 5-gm tube | For use on intact skin | ||||
| *Institutional Cost at Children's Hospital; Columbus, Ohio | |||||
One of the most widely used and widely studied topical anesthetic agents is TAC solution (tetracaine 0.5%, epinephrine 1:2,000, cocaine 11.8%). Cocaine has properties that make it useful in anesthetic compounds. Not only does it provide analgesia by blocking impulse conduction in the sensory nerves, cocaine is also a mild vasoconstrictor and thereby potentiates its own anesthetic effect.6 In 1980, Pryor and colleagues introduced one of the first prospective, randomized studies comparing the use of TAC solution to lidocaine injection for minor laceration repair.18 The study reported no difference in anesthetic efficacy or wound complication rates, and found shorter repair times when TAC was used instead of lidocaine. TAC can be applied without pain and does not distort wound margins. TAC works best on facial and scalp lacerations and is less effective on the trunk and extremities. When applied to a laceration, the solution should be pooled in the wound and then applied to wound margins with a cotton-tipped swab. The remainder of the solution is applied with a cotton ball and pressed against the laceration. Gauze should be avoided because the solution will absorb into the gauze and limit its absorption into the wound. The solution should be applied for 20-30 minutes prior to use. Studies have shown TAC to be almost 90% effective in providing analgesia for minor wound repair.19
The use of TAC has simplified wound repair and significantly decreased the pain experienced by patients. There are, however, important side effects and other considerations with its use. The use of cocaine in the compound necessitates that schedule II drug regulations be followed. The compound must be secured and its use documented carefully by medical staff. The use of cocaine significantly increases the cost of the medication. A single dose of TAC solution costs about $17 (institutional cost), approximately 10 times more expensive than an injection of lidocaine.16 The onset of TAC is slower than that of lidocaine. Analgesia may begin at 5 minutes but acceptable analgesia is not usually reached for 20-30 minutes. Once anesthetized with TAC, pain control is usually adequate for up to one hour.
The issue of primary concern regarding the use of TAC is its potential for toxicity. Even with appropriate use of TAC, side effects can occur. Adverse effects are almost entirely due to the toxicity of cocaine. Most problems are the result of inadvertent mucosal application or misuse of the product. The most common side effects are agitation, tachycardia, and pupillary dilatation. More serious complications include apnea, seizures, and even death.20,21 Cocaine produces its toxic effects on the cardiovascular system by inhibiting reuptake of catecholamines, which can lead to increased blood pressure and ventricular dysryhthmias. Blood and urine screens may turn positive for cocaine and its breakdown products even without clinical signs of toxicity. Mucosal surfaces should be avoided and the solution should not be used on lacerations greater than 4 cm in length or areas with burned or abraded skin, as this can increase the systemic absorption of cocaine. Older recommendations for dosing of TAC advised applying 1 mL of solution per 1 cm wound length, to a maximum 3-4 mL. In an attempt to limit toxicity, newer recommendations suggest using 1 mL solution per 10 kg body weight with a maximum of 3 mL. Toxicity studies involving cocaine suggest that no more than 100 mg of cocaine should be applied topically. One mL of 11.8% solution contains 118 mg of cocaine.22
With increasing awareness of the potential toxicity of cocaine, newer studies have looked at the efficacy of TAC solution with lesser concentrations of cocaine. Several studies have shown that lowering the concentration does not diminish its analgesic efficacy. Compounds with 4% and 5.9% cocaine instead of 11.8% have been shown to produce equal anesthesia for laceration repair and decrease the likelihood of adverse effects.16,23,24 Removing the cocaine from the compound entirely, however, does decrease its potency.
Newer topical agents are being developed to offer alternatives to the use of cocaine. Blackburn and colleagues showed that topical lidocaine and epinephrine applied to a wound for 20 minutes had equal anesthesia to TAC. 25 Stewart and associates studied the efficacy of soaking a Telfaâ pad with 1% lidocaine and applying it topically to a laceration in an attempt to reduce the pain from subsequent lidocaine injection.7 The lidocaine alone did not provide sufficient analgesia when used topically. The addition of a vasoconstrictor is felt to be necessary to enhance the anesthetic potential.
An important new compound is LET gel (lidocaine 4%, epinephrine 0.1%, and tetracaine 0.5%). As with TAC solution, it is used for minor lacerations on the face and scalp. It is not indicated for use on mucous membranes. Studies have shown that when applied topically, the adequacy of anesthesia before suturing and duration of anesthesia during wound closure is comparable to TAC.19,26 Because the cocaine is removed, the cost is significantly less and comparable to the cost of lidocaine injection. No records need to be maintained for schedule II drug use, and most importantly, the potential toxicity of cocaine is eliminated.
The preparation of LET gel can be a time-consuming process for a pharmacy staff. However, it may be prepared in bulk and stored in individual 3-mL dose syringes. If the gel is refrigerated, it has a shelf life of five months. LET gel is applied similarly to TAC; a small amount should be applied directly to the wound and the remainder applied on a cotton ball for 20-30 minutes. The use of LET gel vs. LET solution was studied by Resch and colleagues. The anesthetic action of the two compounds is similar, however, the gel form is significantly easier to use. The solution tends to run out of the wound and is more likely to contaminate mucous membranes or ocular structures. The gel form keeps the anesthetic agent better contained than the solution and tends to remain in place.27
Other new topical agents without cocaine are being developed. Smith and colleagues studied the efficacy of four compounds containing different amide anesthetics and vasoconstrictors. Bupivanor bupivacaine-norepinephrine was found to provide analgesia as effectively as TAC or 1% lidocaine.28
A new area of study is the use of topical anesthetic compounds on or near mucosal surfaces. There are currently no topical agents that have been demonstrated to be safe and effective for repair of mucous membrane lacerations. Smith and associates have conducted two studies with topicals used on or near mucosal surfaces.29,30 The first study used tetralidophen (tetracaine, lidocaine, phenylephrine) as the anesthetic agent. It was evaluated for lacerations primarily around the eyes and lips. Tetralidophen was found to be statistically inferior for analgesia when compared to lidocaine injection. A similar study used prilophen (prilocaine, phenylephrine) and also found it to be less effective than lidocaine. In both of these studies, however, the differences in pain scores were small and may not be clinically significant. Furthermore, the pain associated with lidocaine injection was not taken into account. Lacerations involving mucous membranes are common, and it is hoped that continued research with topical anesthetics will lead to the development of new agents that are both safe and effective for use in these locations.
There are shortcomings to the use of topical anesthetics. They have a significantly longer time to onset of analgesia and an overall shorter duration of anesthetic action than tissue infiltration. Topicals are ineffective on the trunk and extremities because of comparatively diminished blood flow in these areas.
Patients may have incomplete analgesia with topicals, even when used on the face and scalp. Topical anesthetic agents cost more to use than infiltrative drugs. This is especially true of the compounds which contain cocaine.16 Newer agents that don’t include cocaine are significantly less expensive and are comparable to the cost of lidocaine injection. Concern has been raised about the incidence of wound infection with topical agents. It is postulated that vasoconstriction at the wound site leads to local tissue hypoxia, which may interfere with wound healing and increase the likelihood of infection.17 Although this may be an area for future research, none of the current studies using topical agents have reported an increased incidence of infection. Topical agents should not be used close to the eye, as inadvertent systemic absorption can occur as well as corneal abrasion from irritation. Topicals that contain vasoconstrictor agents should be kept from areas of end-arteriolar blood supply to avoid tissue ischemia. Finally, there are no topical agents available that are recommended for use on or near mucosal surfaces. Although new products are being studied, lidocaine infiltration is still the standard for lacerations involving the mucous membranes.
Eutectic Mixture of Local Anesthetics (EMLA) cream has become widely used in the United States in the last decade. EMLA is composed of 2.5% lidocaine and 2.5% prilocaine, both amide anesthetics.5,6 The compound is soluble in equal proportions in both the solid and fluid phases, thereby promoting rapid absorption. Its primary use is on intact skin for minor procedures including venipuncture, lumbar puncture, and minor dermatologic excisions. Recently, it has been studied in newborn circumcision and other procedures in neonatology.31 Although the compound does provide adequate analgesia, its time to onset makes its use impractical for laceration repair. The cream is ideally applied for 45-60 minutes to be effective. A unique side effect with prilocaine is that it can oxidize hemoglobin to methemoglobin. Benzocaine and nitric oxide as well as a few other drugs also have this effect. There have been reports of methemoglobinemia in neonates who have had the drug applied to a large surface area for a prolonged period of time.5 Finally, there is concern that EMLA may interfere with wound healing, and so it is not indicated for laceration repair.
Tissue Adhesives
In addition to the development and use of topical anesthetic agents, the introduction of tissue adhesives for laceration repair has created a revolution in wound management. Traditional sutures will always have a role in wound repair, however, in selected circumstances, adhesives are an important alternative. Early and effective wound repair helps to restore the protective barrier of the skin. It enhances the healing process and limits the risk of infection. Of all lacerations that occur in children, one-half occur in patients younger than 5 years of age. 2 The head is the most common site of lacerations in children (60%), followed by upper extremities (23%) and lower extremities (15%). Children younger than age 2 are especially likely to present with lacerations to the head, face, and chin. 32
The use of tissue adhesives can offer several advantages to traditional sutures. They are painless, easily applied, require minimal training, and significantly decrease the time required for laceration repair. Further, because of the decreased time and supplies needed, the costs associated with the use of adhesives are less than those with sutures. Finally, perhaps the most important consideration with laceration repair is the final appearance of the wound. Several studies comparing the use of adhesives to sutures report equal cosmetic outcome, and in some cases, improved cosmesis with the use of adhesives.
The adhesive products that have been developed for wound repair belong to the class of compounds called cyanoacrylates. The technology behind cyanoacrylate tissue adhesives was developed almost 50 years ago. Clinically, they were introduced in the 1950s and used as surgical adhesives. Since that time they have been used in multiple surgical procedures including plastic surgery, head and neck procedures, skin and bone grafts, and corneal and eyelid surgery.33 They have been used for laceration repair in Canada since 1975 and have been widely used in Europe, Israel, and the Far East for many years.
Cyanoacrylates are organic liquid monomers that polymerize on contact with moisture on the skin’s surface.34 When applied correctly to the outermost layer of skin, a film is formed over the edges of a wound creating a strong bond allowing healing to occur. The first two compounds produced were methyl-2-cyanoacrylate and ethyl-2-cyanoacrylate (marketed as Krazy Glue, Borden, Columbus, OH). These adhesives had strong binding capabilities but caused excessive tissue toxicity leading to both acute and chronic inflammation around the area of use. The short alkyl chain on these compounds degrades quickly, resulting in accumulation of the breakdown products formaldehyde and cyanoacetate which are tissue toxic. The newer adhesives have longer alkyl chains. Breakdown is slower and the metabolites are cleared before toxicity results.35
Specific Agents
The first of the newer cyanoacrylate compounds to be developed specifically for laceration repair was N-Butyl-2-cyanoacrylate or Histoacryl Blue (HAB). Although not approved for use in the United States, it has been used extensively in Canada for many years. In addition to its ease of application, it has been demonstrated to provide good tensile strength and have limited toxicity.34 HAB is packaged in a 0.5-mL vial that costs approximately $22.36 Although marketed for individual use, because of the process used to apply HAB, these vials may be reused and have enough adhesive for 10-12 applications. Glustitch is a newer N-2-butyl-cyanoacrylate adhesive. It has the same spectrum of use as HAB. It is available for purchase in the United States but is not promoted for wound closure. 2-Octylcyanoacrylate (Dermabond, Ethicon Inc, Somerville, NJ) was approved for use in laceration repair in 1998.37 It is the first medical-grade adhesive approved for use in the United States. The older butyl-derivative compounds have not received this medical-grade designation, which is given to those products that meet the FDA standard for non-toxic medical devices. 2-Octylcyanoacrylate (2-OCA) has several important advantages over the older compounds. The monomer in 2-OCA has been combined with a plasticizer which makes it more flexible and less likely to crack. The tensile strength of 2-OCA is 3-4 times greater than that of HAB and is comparable to that of 5-0 sutures.34,35 2-OCA is packaged in single use 0.5-mL ampules with applicator tips. It has a shelf life of about two years. The cost per ampule is about $25.
As with any new product, satisfaction and comfort with the use of adhesives can be attained by using the same approach with each wound and following a few guidelines specific to their use. (See Table 2.) After thorough wound cleansing, 2-OCA is applied by lightly brushing the liquid over the opposed edges of the wound. With experience, one person may be able to oppose the edges and apply the adhesive. With less cooperative patients or more complicated lacerations, it may be helpful to have a second person available for patient stabilization and wound margin approximation. Tissue forceps are available to help with closure. As the adhesive is applied it should be brushed in an elliptical pattern over the wound; at least three layers are recommended. The wound margins are then held together for approximately 30-60 seconds while the bond forms. Some users find that 2-OCA may be a bit "runny" when it initially flows from the ampule. Once the ampule is cracked, the liquid should be allowed to fill the cotton-tipped applicator. At this time, it is helpful to release pressure on the ampule and wait several seconds before beginning wound closure. This allows the liquid to thicken slightly and helps prevent run-off of the product away from the wound. Another way to prevent run-off is to keep the surface of the wounds as flat as possible during application of adhesive. When using HAB, the adhesive is applied using a 27-gauge needle. HAB is placed as beads of liquid intermittently along the length of the laceration. It is not brushed over the surface as 2-OCA. In a study evaluating the attainment of proficiency with adhesive use, Hollander and associates found that physicians can develop competence with the use of 2-OCA after only a brief training period.38 Prior studies have demonstrated an improvement in cosmetic outcome and decreased wound infection rates for traditional suturing as physician experience grows. Cosmetic outcome was evaluated in wounds closed with adhesives by practitioners with varying levels of experience. Outcome did not improve as the physicians gained experience with the adhesive, suggesting that its use is readily learned.38 There are, however, nuances in the application of 2-OCA which when mastered, can enhance the final appearance of a wound and the satisfaction of the medical staff using the product. While it is likely that providers who use adhesives on a regular basis will achieve a level of comfort with the product, it remains to be seen if those who rely on the use of adhesives only a few times each year will be as comfortable with their use.
| Table 2. Application Guidelines for the Use of Tissue Adhesives | |||||
| 1. Consider application of topical anesthetic agent 20-30 minutes prior to wound repair. | |||||
| 2. Inject wound with local anesthetic as needed for thorough cleaning and repair. | |||||
| 3. Cleanse wound thoroughly, irrigate, and debride as indicated. | |||||
| 4. Keep wound flat, wipe away any blood or blood clots. | |||||
| 5. Crack inner ampule of 2-OCA, allow liquid to fill the applicator (until tip turns purple). | |||||
| 6. Release pressure on ampule and wait several seconds, allowing the liquid to thicken slightly. | |||||
| 7. Approximate wound edges with fingers or tissue forceps. | |||||
| 8. Apply one layer of adhesive lengthwise across the surface of the wound. Hold the wound margins together for several seconds. | |||||
| 9. Apply 4-5 layers of very thin adhesive in an ellipitical pattern over the surface of the wound beginning centrally and working outward. Each layer should cover a slightly larger surface area than the previous layer. | |||||
| 10. Let the adhesive bond strengthen and set for up to ~1 minute. | |||||
| 11. Consider covering the wound if in an area likely to be fingered by a child. | |||||
Complications
Because of the rapid bonding that occurs with adhesives, mishaps may occur during their use. It is not uncommon to attach an exam glove to the outer aspect of a wound during closure. Once the wound is closed, the glove may be trimmed and the attached piece will fall off as the adhesive flakes off in 7-10 days. Lanolin, petroleum jelly, or acetone may also be used to remove adhesive. Water and cleansers such as betadyne will not be effective immediately. Adhesives should be used cautiously on surfaces surrounding the eyes. Adhesive may drip into the lashes when used on wounds within the margin of the eyebrow. If contact with the eye occurs, the eye should be flushed thoroughly. For adhesive on lashes or the eyelid, topical ophthalmic ointments may be applied to help loosen the bond. Ointment may be applied to the lashes prior to use of the adhesive to prevent unintentional bonding of the eyelashes or eyelid. Parents should be advised that it is acceptable to shower and cleanse around the wound; however, the wound itself should not be soaked. Repetitive washing or exposure to moisture will weaken the closure. For the same reason, topical antibiotic ointments should not be applied.
Complications can arise with the use of tissue adhesives, even when used appropriately. First of all, the initial strength of a wound closed with adhesive is less than that of a laceration closed with sutures. The strength of the wound on the first day of closure is only 10-15% of the strength of a wound closed with traditional sutures.35 One week after closure the strength of the wounds are equal. By this time, the healing process is well underway. As a result, early dehiscence is the most common complication with adhesive use. Most wounds can be re-closed primarily with either adhesive or sutures unless a prolonged period of time has passed between wound dehiscence and presentation for care.
Infection can occur with any wound. Concern for an increased rate of wound infection with tissue adhesives may cause some practitioners to limit its use. There are no data to support an increased risk of infection with the use of adhesives. In a study by Howell and colleagues the butyl-derivative compounds were actually shown to have a bacteriostatic effect against Staphylococcus aureus.39 Adhesives should not be used in areas with active infection, or for wounds that are heavily contaminated and require excessive cleaning or debridement. Adhesives are not recommended for use on animal or human bites, puncture wounds, or stellate or crush wounds.38 (See Table 3.) The ease with which adhesives are applied should never jeopardize the need for thorough wound cleansing. Contaminated wounds may require the use of local anesthesia for proper wound irrigation and exploration before adhesives are applied. Thorough wound cleansing and judicious use of adhesives should minimize the risk for infection. If infections do occur, they may be treated in the same manner as those with sutured wounds. Some wounds may need to be opened to allow drainage and oral antibiotics with coverage for common skin flora may be prescribed.
| Table 3. Wound Types Contraindicated for Use of Tissue Adhesives | |||||
| • Puncture wounds | |||||
| • Animal or human bites | |||||
| • Heavily contaminated wounds | |||||
| • Wounds with active infection or gangrene | |||||
| • Stellate or crush wounds | |||||
| • Wounds with length greater than 4-6 cm | |||||
| • Wounds gaping greater than 4-6 cm | |||||
Tissue adhesives may crack and fragment along the length of a laceration before healing is complete. This is much more common with the butyl-derivative compounds than with 2-OCA.35 Current recommendations are to restrict the use of adhesives to wounds less than 4-6 cm in length. Cracking of the adhesive is also more likely when used over joints or areas of high friction. If adhesive is used to close a wound over a joint, the area should be splinted to reduce the risk of dehiscence.39 (See Table 4.) Children may pick at the adhesive and loosen the bond prematurely. One of the advantages of adhesives is the ability to leave the wound uncovered, thereby observing for any signs of infection. The wound may be covered for protection, however, if it is in an area likely to be manipulated at by a child.
| Table 4. Areas Contraindicated for Use of Tissue Adhesives | |||||
| • Areas of high skin tension (joints) | |||||
| • Areas subjected to repetitive friction (hands, feet) | |||||
| • Areas of prolonged moisture (mucosal surfaces, mucocutaneous junctions) | |||||
| • Areas with dense hair | |||||
Despite the longer alkyl chain in the newer compounds, some tissue toxicity may occur with adhesives. Both mild acute and chronic inflammation have been reported. This is especially likely to be seen in well-vascularized areas. Applying adhesive only to the outer surface of the wound can minimize inflammation. When adhesive is incorrectly placed within the wound, it can lead to a foreign-body reaction and possibly result in poor wound healing.35 It is important to wipe away any blood or blood clots from the surface of the wound prior to application of the adhesive as this, too can interfere with wound margin approximation and affect the closure of a laceration.
A final complication with the use of tissue adhesives is that the polymerization is an exothermic reaction. Heat is released as the bond is formed over the wound. Some patients may report a slight burning sensation as the adhesive is applied.36
Several studies have been conducted in the past few years comparing the use of tissue adhesives to the use of traditional sutures in laceration repair. HAB is the most widely studied compound because it has been used clinically for a longer period of time. Bruns and associates studied wound repair using HAB in children. HAB was reported to offer a significant savings in time; repair took an average of 7 minutes in the HAB group compared to 17 minutes in the suture group. Parental perception of their child’s pain was less in the HAB group and parents were more likely to recommend HAB to other parents and guardians. No difference in complication rates was noted. Finally, cosmetic outcome was evaluated at two months after injury and there was no difference in the appearance of wounds with either method of closure.33 In a follow-up study, the long-term appearance of the wounds was evaluated. By one year after injury, the collagen in a wound has completely matured and is close to 100% of its original tensile strength. Other studies regarding wound repair have shown that wounds change significantly within the first three months after injury. Appearance of a wound at one year, however, is a good representation of its final appearance.40 Wounds closed with HAB were found to be cosmetically similar to those closed with traditional sutures one year after injury.41
Studies evaluating the use of the newer adhesive 2-OCA are fewer in number but have similar findings. In separate studies, 2-OCA was found to be a faster method of wound closure and less painful than traditional sutures.34,35 Again, there was no difference in wound complication rates and 95% of parents whose children were treated with 2-OCA would choose this same method of closure in the future. There were no differences in the cosmesis scores between the different treatment groups at three months after injury. A one-year follow-up study involving 2-OCA was conducted and the long-term cosmetic outcome was found to be equal for lacerations closed with adhesive as compared to those closed with sutures.42 All of these studies were conducted on similar types of wounds. Lacerations were excluded from these studies if they were heavily contaminated, caused by animal or human bites, or located on the scalp or mucocutaneous junctions. Puncture wounds, lacerations longer than 4 cm, and wounds in patients with underlying chronic medical conditions were also routinely excluded. Further research is warranted with adhesives in these and other special circumstances to help delineate future indications and limitations for their use.
Another aspect of wound closure and cosmetic outcome was addressed in a study by Simon and colleagues.43 Cosmetic outcome using adhesives and sutures was evaluated taking the initial orientation of the wound into account. Langer’s Lines define the functional anatomy of the structures underlying the skin. Wounds that are oriented along Langer’s Lines (Langer +) have been found to have a better cosmetic outcome when compared to those oriented against Langer’s Lines (Langer -). In this study, there was a difference in the cosmetic outcome of sutured wounds depending on original orientation. The wounds closed with adhesive, however, were found to have a similar cosmetic outcome regardless of orientation.
The author raised the idea that adhesives may become the preferred method of closure for appropriate wounds with orientation against Langer’s Lines.43
An important consideration with the use of adhesives is their economic impact on medical care. Early studies are demonstrating that the efficacy, complication rate, and cosmetic outcome are approximately equal with adhesives and traditional sutures. Clinicians are becoming increasingly aware of issues relating to medical costs and third-party payers. The economic benefits of adhesives should not be overlooked. In a study by Osmond and colleagues the incremental costs of wound closure using tissue adhesives, absorbable sutures, and non-absorbable sutures were compared.44 The non-dissolving suture group was found to have the highest costs and the tissue adhesive group had the lowest. The cost of follow-up visits including physician fees and parental lost wages are felt to be the main reason for this increased cost. Furthermore, there was less consumption of materials and less time required for repair in the adhesive group. In a willingness-to-pay survey it was reported that parents were willing to pay more out-of-pocket expenses for the use of tissue adhesives.44 Parents value this method of closure because of differences in perceived pain and psychologic trauma to their children.
The Physician’s Current Procedural Terminology (CPT) guidelines for physician billing currently recognize four levels of treatment for wound care. The most simple is "minimal" closure, which includes the use of Steri-strips. This is included in the evaluation and management (E&M) code. Until recently, the other levels of wound closure (simple, intermediate, and complex) did not specifically recognize the use of tissue adhesives. For wounds closed with adhesives, it was recommended to use the unlisted code, 17999 (unlisted procedure, skin, mucous membrane, and subcutaneous tissue). A recent change to the guidelines has been made to include the use of adhesives in the original codes for wound closure. Closure by sutures, staples, and tissue adhesives will now fall under the same category. The majority of wounds repaired with adhesives will be at the "simple" level of billing. This represents a single-layer closure without the need for excessive cleaning or debridement. "Intermediate" closure would be consistent with wounds that require subcutaneous sutures (even if adhesive is used for the outermost layer of skin). Finally, "complex" wounds require significant cleaning, debridement, or wound revision. Because of their high-risk nature, these wounds will rarely be closed with adhesives. The CPT guidelines published in the year 2000 will contain these revised codes.45
Conclusion
The management of minor wounds in children will undoubtedly remain an important part of pediatric care in the future. There can be great satisfaction on the part of clinicians and great relief on the part of parents and children when lacerations are repaired accurately, efficiently, and with as little additional pain as possible. New products and new techniques are constantly being developed to help reach these goals. Topical anesthetic agents and tissue adhesives promise to make an important contribution to pediatric wound management. As with any new product, it is imperative that the care-providers using topical anesthetics and adhesives educate themselves and their patients about the appropriate use as well as the limitations of these products. Continued research in wound management is warranted to help define these areas. With judicious use, topical anesthetics and tissue adhesives may safely and effectively be incorporated into the practice of pediatric care providers.
References
1. Stussman BJ. National Hospital Ambulatory Medical Care Survey: 1994 Emergency Department Summary. Advance Data from Vital and Health Statistics; no. 275. Hyattsville, MD: National Center for Health Statistics, 1996;DHS publication no. PHS 96-1250.
2. McNamara R, Loiselle J. Laceration Repair. In: Henretig, FM, King, C, et al, eds. Pediatric Emergency Procedures. Baltimore: Williams and Wilkins; 1997:1141-1168.
3. Altman RS, Smith-Coggins R, Ampel LL. Local Anesthetics. Ann Emerg Med 1985;14:1209-1217.
4. Di Fazio CA. Local Anestheics: Action, Metabolism and Toxicity. Oto Clin North Am 1981;14:515-519.
5. Berde CB. Toxicity of Local Anesthetics in Infants and Children. J Peds 1993;122:514-520.
6. Lewis L, Stephan M. Local and Regional Anesthesia. In: Henretig FM, King C, et al, eds. Pediatric Emergency Procedures. Baltimore: Williams and Wilkins; 1997:465-496.
7. Stewart GM, Simpson P, Rosenberg NM. Use of Topical Lidocaine in Pediatric Laceration Repair: A Review of Topical Anesthetics. Ped Emerg Care 1998;14:419-423.
8. Physician’s Desk Reference, 53rd ed. Montvale, NJ: Medical Economoics Co., Inc.; 1999:559,603.
9. Yan AC, Newman RD. Bupivacaine-Induced Seizures and Ventricular Fibrillation in a 13-Year-Old Girl Undergoing Wound Debridement. Ped Emerg Care 1998;14:354-355.
10. Adriani J, Zepernick R. Allergic Reactions to Local Anesthetics. Couth Ned J 1981;74:694-499.
11. Bartfield JM, Gennis P, Barbera J, et al. Buffered Versus Plain Lidocaine as a Local Anestheic for Simple Laceration Repair. Ann Emerg Med 1990;19:1387-1389.
12. Wilson L, Martin S. Benzyl Alcohol as an Alternative Local Anesthetic. Ann Emerg Med 1999;33:495-499.
13. Lugo-Janer G, Padial M, Sanchez JL. Less Painful Alternatives for Local Anesthesia. J Dermatol Surg Oncol 1993;19:237-240.
14. Ernst AA, Anand P, Nick T, et al. Lidocaine Versus Diphenhy dramine for Anesthesia in the Repair of Minor Lacerations. J Trauma 1993;34:354-357.
15. Bartfield JM, Jandreau SW, Raccio-Robak N. Randomized Trial of Diphenhydramine Versus Benzyl Alcohol with Epinephrine as an Alternative to Local Anesthesia. Ann Emerg Med 1998;32:650-654.
16. Vinci J, Fish SS. Efficacy of Topical Anesthesia in Children. ArchPed Adol Med 1996;150:466-469.
17. Martin JR, Doezema D, Tandberg D, et al. The Effect of Local Anesthetics on Bacterial Proliferation: TAC Versus Lidocaine. Ann Emerg Med 1990;19:987-990.
18. Pryor GJ, Kilpatrick WR, Opp DR, et al. Local Anesthesia in Minor Lacerations: Topical TAC vs. Lidocaine Infiltration. Ann Emerg Med1980;9:568-571.
19. Schilling CG, Bank DE, Borchert BA, et al. Tetracaine, Epinephrine Adrenalin and Cocaine TAC Versus Lidocaine, Epinephrine, and Tetracaine LET for Anesthesia of Lacerations in Children. Ann Emerg Med 1995;25:203-208.
20. Terndrup TE, D’Agostino J. Pain Control, Analgesia and Sedation. In: Barkin RM, et al, eds. Pediatric Emergency Medicine Concepts and Clinical Practice. 2nd ed. St. Louis: Mosby; 1997: 48-67.
21. Selbst SM. Sedation and analgesia. In: Fleisher GR, Ludwig S, et al, eds. Textbook of Pediatric Emergency Medicine. 3rd ed. Baltimore: Williams and Wikins; 1993:55-64.
22. Barnett P. Cocaine Toxicity Following Dermal Application of Adrenaline-Cocaine Preparation. Ped Emerg Care 1998;14:280-281.
23. Smith SM, Barry RL. A comparison of Three Formulations of TAC for Anesthesia of Minor Lacerations in Children. Ped Emerg Care 1990;6:266-269.
24. Bonadio WA, Wagner V. Half-Strength TAC Topical Anesthesia. Clin Ped 1988;27:495-498.
25. Blackburn PA, Butler KH, Hughes MJ, et al. Comparison of Tetracaine-Adrenaline-Cocaine TAC with Lidocaine-Epinephrine TLE: Efficacy and Cost. Am J Emerg Med 1995;13:315-317.
26. Ernst AA, Marvez E, Nick TG, et al. Lidocaine-Adrenaline-Tetracaine Gel Versus Tetracaine-Adrenaline-Cocaine Gel for Topical Anesthesia in Linear Scalp and Facial Lacerations in Children Aged 5-17 Years. Pediatrics 1995;95:255-258.
27. Resch K, Schilling C, Borchert BD, et al. Topical Anesthesia for Pediatric Lacerations: A Randomized Trial of Lidocaine-Epinephrine-Tetracaine Solution Versus Gel. Ann Emerg Med 1998 ;32: 693-697.
28. Smith GA, Strausbaugh SD, Harbeck-Weber C, et al. Comparison of Topical Anesthetics Without Cocaine to Tetracaine-Adrenaline-Cocaine and Lidocaine Infiltration During Repair of Lacerations. Pediatrics 1996;97:301-307.
29. Smith GA, Cohen DM, Strausbaugh SD, et al. Tetracaine-Lidocaine-Phenylephrine Topical Anesthesia Compared with Lidocaine Infiltration During Repair of Mucous Membrane Lacerations in Children. Clin Pediatr 1998;37:405-412.
30. Smith GA, Strausbaugh SD, Harbeck-Weber C, et al. Prilocaine-Phenylephrine Topical Anesthesia for Repair of Mucous Membrane Lacerations. Ped Emerg Care 1998;14:324-329.
31. Taddio A, Ohlsson A, Einarson TR, et al. A Systematic Review of Lidocaine-Prilocaine Cream EMLA in the Treatment of Acute Pain in Neonates. Pediatrics 1998;101:299.
32. Baker MD, Selbst SM, Lanuti M. Lacerations in Urban Children: A Prospective 12-January Study. AJDC 1990;144:87-92.
33. Bruns TB, Simon HK, McLario DJ, et al. Laceration Repair Using a Tissue Adhesive in a Children’s Emergency Department. Pediatrics 1996;98:673-675.
34. Bruns TB, Robinson BS, Smith RJ, et al. A New Tissue Adhesive for Laceration Repair in Children. J Pediatr 1998;132:1067-1070.
35. Quinn J, Wells G, Sutcliffe T, et al. A Randomized Trial Comparing Octylcyanoacrylate Tissue Adhesive and Sutures in the Management of Lacerations. JAMA 1997;277:1527-1530.
36. Quinn JV, Drzewiecki A, Li MM, et al. A Randomized, Controlled Trial Comparing Tissue Adhesive with Suturing in the Repair of Pediatric Facial Lacerations. Ann Emerg Med 1993;22:1130-1135.
37. Mechcatie E. Wound Glue Gets FDA Panel’s Nod. Pediatric News 1998;32:15.
38. Hollander JE, Singer AJ, et al. Application of Tissue Adhesives: Rapid Attainment of Proficiency. Acad Emerg Med 198 ;5:1012-1017.
39. Howell JM, Bresnahan KA, Stair TO, et al. Comparison of Effects of Suture and Cyanoacrylate Tissue Adhesive on Bacterial Counts in Contaminated Lacerations. Antimicrob Agents Chemother 1995;39:559-560.
40. Peacock EE. Collagenolysis and the Biochemistry of Wound Healing. In: Peacock EE, ed. Wound Repair, 3rd ed. Philadelphia, PA: WB Saunders; 1984:102-140.
41. Simon K, McLario DJ, Bruns TB, et al. Long-Term Appearance Using a Tissue Adhesive. Pediatrics 1997;99:193-195.
42. Quinn J, Wells G, Sutcliffe, et al. Tissue Adhesive Versus Suture Wound Repair at One Year: Randomized Clinical Trial Correlating Early, 3 Month and One Year Cosmetic Outcome. Ann Emerg Med 1998;32:645-649.
43. Simon HK, Zempsky WT, Bruns TB, et al. Lacerations Against Langer’s Lines: To Glue or Suture? J Emerg Med 1998;16: 185-189.
44. Osmond MH, Klassen TP, Quinn JV. Economic Comparison of a Tissue Adhesive and Suturing in the Repair of Pediatric Facial Lacerations. J Pediar 1995;126:892-895.
45. The Physician’s Current Procedural Terminology Handbook. Harris, TR, Vice-Chair Editorial Committee, American Medical Association. Chicago, IL; 1999.
Physician CME Questions
14. Which of the following is felt to be most responsible for the pain associated with injection of lidocaine?
a. The acidic pH of the medication
b. The rate of diffusion of medication into the cells
c. The temperature of the medication
d. The amide bond in the structure of the medication
15. The use of benzyl alcohol is limited as an anesthetic agent because:
a. benzyl alcohol does not provide adequate analgesia.
b. benzyl alcohol is more painful on injection than lidocaine.
c. the use of benzyl alcohol is associated with a high incidence of toxicity.
d. the duration of analgesia with benzyl alcohol is brief.
16. Current recommendations regarding the use of TAC solution include:
a. applying the solution for 5-10 minutes prior to use.
b. applying 1 mL of solution per 1 cm length of wound.
c. limiting topical application to 100 mg of cocaine.
d. use for lacerations on the trunk and extremities.
17. Which of the following is true regarding the use of topical anesthetic agents?
a. Topical agents are effective on wounds involving the trunk and extremities.
b. The addition of a vasoconstrictor is necessary to potentiate the action of topical anesthetics.
c. Topical agents are associated with an increased risk of wound infection.
d. Wound margin distortion occurs with topical agents as it does with lidocaine injection.
19. What advice is appropriate for patients with wounds closed with adhesives?
a. Thorough washing of the wound is recommended after closure.
b. Topical antibiotic ointments may be safely applied to the wound after closure.
c. Adhesives usually flake off two weeks after application.
d. Adhesives can be removed with petroleum jelly or acetone.
20. Which factor best explains the increased cost for wounds closed with sutures compared to those closed with adhesives?
a. The cost of supplies required for wound repair
b. The cost of follow-up visits and parental lost wages
c. The cost of physician time for wound repair
d. The difference in insurance reimbursement for wound repair
21. Which of the following is true regarding application of tissue adhesives?
a. Adhesives should only be applied to the outermost layer of skin.
b. One layer of adhesive is adequate for closure of simple wounds.
c. Adhesives may be safely used on mucous membrane lacerations.
d. Adhesives are preferred over sutures for human and animal bites.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.