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Clinical profile of cutaneous drug reactions.

Byline: L Khondker AND MSI Khan

Abstract Objective To find out the clinical profile of cutaneous drug reactions in a tertiary level hospital.

Methods In this cross-sectional study carried out for a period from January 2011 to December 2011 data were collected from the Department of Dermatology and Venereology Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka Bangladesh. Patients suffering from adverse drug reactions were the study population and within the period of data collection twenty patients were selected.

Results Out of total twenty patients 9 (45%) had fixed drug eruptions 4 (20%) urticaria 3 (15%) Stevens-Johnson syndrome 2 (10%) morbilliform rashes and 2 (10%) had erythema multiforme. The most common clinical presentation was hyperpigmented macule/patch in 5 (25%) cases followed by urticarial plaque 4 (20%) erosive lesion 3 (15%) and loss of skin in sheets less than 10% body surface area 3 (15%) and morbilliform rashes and target lesions in 2(10%) each. 6 (30%) patients developed mucosal involvement only and majority of them 8 (40%) had oral involvement. The most common type of offending drug causing the drug reactions were sulfur containing drugs in 8 (40%) cases followed by NSAIDs in 6 (30%) quinolones 3 (15%) metronidazole and anticonvulsants in a few.

Conclusion The common types of cutaneous drug eruptions are fixed drug eruptions urticaria Stevens-Johnson syndrome morbilliform rashes and erythema multiforme.

Key wordsClinical profile adverse drug reactions.

Introduction Drug reactions are a common cause of dermatologic consultation. The majority of cutaneous drug reactions are exanthematous (75%-95%) and urticarial (5%-6%).12 Drug reactions are a major cause of patient morbidity and account for a significant number of patient deaths. Drug reactions may be solely limited to the skin or they may be part of a systemic reaction such as drug hypersensitivity syndrome or toxic epidermal necrolysis.3 Cutaneous drug reactions have become very common in recent times. The incidence of cutaneous drug reactions is about 2.2%.4 Although majority of adverse drug reactions are minor and are self-limiting sometimes severe and potentially life threatening situations like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) can arise which constitute from 2.6% to 7% of all drug reactions. The prevalence of cutaneous drug reactions varies from 15 to 30%.5

Cutaneous drug reactions can be caused by a wide variety of agents. Many of the commonly used drugs have reaction rates above one percent.6 TEN is the most serious of the cutaneous drug reactions. The onset is usually acute and epidermal necrosis involves greater than 30% of body surface area. It can be distinguished from SJS where the total surface of body surface area detachment is less than 10% by definition.7 A morbilliform rash is the most common reaction to phenytoin occurring in as many as 5% of cases overall. However a wide variety of cutaneous reactions can occur including fixed drug eruptions exfoliative dermatitis erythema multiforme SJS vasculitis acneiform lesions and lupus-like reaction.

The drugs capable of producing fixed eruptions are tetracyclines sulphonamides (including co- trimoxazole) barbiturates hyoscine butylbromide ibuprofen dapsone phenolphthalein quinine and derivatives paracetamol benzodiazepines. Erythema multiforme is more commonly precipitated by various interactions and clinically macular papular or urticarial lesions as well as the classical iris or target lesions' on the distal extremities.8 Complicating factors of drug reactions include the myriad clinical symptoms and multiple mechanisms of drug-host interaction many of which are poorly understood. In addition the relative paucity of laboratory testing that is available for drug allergy makes the diagnosis dependent on clinical findings. In future this study deserves to be tried on a large scale with large sample size and in different hospitals in Bangladesh. Information obtained from this study may help in recognizing the magnitude of the disease problem and to take necessary measures to prevent drug reaction.

Methods

It was a cross-sectional study data were collected from the department of Dermatology and Venereology Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka. The study was carried out for a period from January 2011 to December 2011. Patient suffering from adverse drug reaction were selected as study population. Within the period of data collection twenty patients were assigned and consecutive type non-probability sampling techniques were followed in this study. By face to face interview and also from clinical record data were collected from patient. The patient was identified at first. Information was collected by taking medical history and clinical examination and subsequent laboratory investigations. Then clinical conditions of the patient were recorded by the author and skin biopsy was done for histopathological examination. Exclusion criteria included patient unwilling to give informed consent

pregnant and lactating women and patient with severe uncontrolled diabetes mellitus and thyroid disease. Conversely all patients who had given written consent both sexes and from birth to 65 years old ages were included in the study.

Results

Table 1 shows the demographic data and the clinical characteristics of the 20 patients. Out of total 20 9 (45%) had fixed drug eruptions 4 (20%) had urticaria 2 (10%) had morbilliform rashes 2 (10%) erythema multiforme and SJS developed in 3 (15%) cases (Table 2).

The most common clinical presentation was hyperpigmented macules/patches in 5 (25%) cases followed by urticarial plaques in 4 (20%) erosive lesion and loss of skin in sheets (less than 10%) in 3 (15%) and then 2 (10%) cases each had

Table 1 Demographic and clinical characteristics of

patients (n=20).###

Characteristics###N (%)

Age (years)

###10###2 (10)

###11-20###4 (20)

###21-30###8 (40)

###31-40###4 (20)

###greater than 41###2 (10)

Sex###

###Male###14 (70)

###Female###6 (30)

Skin involvement###14 (70)

Mucosal involvement###6 (30)

Table 2 Distribution of patients by common drug

reactions (n=20).

Common drug reactions###N (%)

Fixed drug eruption###9 (45)

Urticaria/Angioedema###4 (20)

Stevens-Johnson syndrome###3 (15)

Erythema Multiforme###2 (10)

Table 3 Distribution of the patients by clinical

presentation (n=20).###

Clinical presentation###N (%)

Hyperpigmented macule/patch###5 (25)

Urticarial wheal###4 (20)

Erosive###3 (15)

Loss of skin in sheets (less than 10%)###3 (15)

Morbilliform###2 (10)

Target lesion###2 (10)

Loss of skin in sheets (greater than 30%)###1 (5)

Table 4 Drugs implicated in the etiology (n=20).

Clinical presentation###N (%)

Sulfonamides###8 (40)

NSAIDs###6 (30)

Quinolones###3 (15)

Metronidazole###2 (10)

Anticonvulsants###1 (5)

morbilliform rashes and target lesions (Table 3). 6 (30%) patients developed mucosal lesions. Oral involvement was seen in 4 (66%) cases ocular and genital mucosal involvement was seen 1 (17%) patient each. The most common offending drugs causing the drug reactions were sulfonamides in 8 (40%) cases followed by NSAIDs in 6 (30%) quinolones in 3 (15%) metronidazole in 2 (10%) cases and anticonvulsants in 1 (5%) case (Table 4).

Discussion

Out of 20 patients in the study 8 (40%) cases were within 21-30 years age group followed by 4 (20%) each of the 11-20 years age group and 31-40 years age group. This differed from the study findings of Patel et al.9 where maximum age group was between 41-50 years old among the 200 patients of adverse drug reaction. The study had similarity with Sharma et al.10 where 50.4% were in the age group of 21-40 years among the 500 patients of adverse drug reactions in Chandigarh India. Among our patients 14 (70%) were male and 6 (30%) were female similar to the study finding of Patel et al.9 where 112 were males and 88 were females. Similar finding was also observed by Sharma et al.10 where 298 (59.6%) were males and 202 (40.4%) were females.

In our study fixed eruption was the most common morphological type. Similar finding was seen by study of Patel et al.9 where 61 (30.5%) had fixed drug eruptions 37 (18%) developed morbilliform eruption 39 (18.5%) of urticaria 25 (12.5%) pruritus Stevens-Johnson syndrome (n=7) erythema multiforme (n=2) and toxic epidermal necrolysis (n=2).9 The study by Ghosh et al.11 reported that majority of adverse reactions were SJS erythema multiforme and urticaria among the 53 patients of adverse drug reactions. The study by Sharma et al.10 also observed that maculopapular rash in 34.6% fixed drug eruptions in 30% and urticaria in 14% among 500 patients of adverse drug reactions in Chandigarh India.

The most common type of offending drugs causing the drug reactions are sulfonamides in 8 (40%) cases followed by NSAIDs in 6 (30%) quinolones 3 (15%) metronidazole in 2 (10%) cases and anticonvulsants in 1(5%) case similar to the study finding of Patel et al.9 where majority of causative drugs in fixed drug reaction were co-trimoxazole 26 (29.5%) and NSAIDs 20 (22.8%) in number. NSAIDs were also the main offenders in causing urticaria angioedema and morbilliform rash.

Conclusion

Although some cutaneous drug reactions are self-limiting but some are dangerous enough even may lead to death if not diagnosed early and not promptly and efficiently treated. Hence each of these cutaneous reactions should be considered with great importance.

References

1.Marc A Riedl MD Adrian M Casillas MD. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003;68:1781- 91.

2. James WD Berger TG Elston D. Andrew's Disease of the Skin-Clinical Dermatology. th10 edition. Philadelphia: Saunders Elsevier; 2006.3. Shear NH Knowles SR Shapiro L. Cutaneous reactions to drugs. In: Wolff K Goldsmith LA Katz SI et al. editors. Fitzpatrick's Dermatology in General Medicine. 8 edition. New York: McGraw Hill Companies; 2003. P.355-61.

4. Ahmad FU Mahapatra AK. Phenytoin- induced toxic epidermal necrolysis in a neurosurgical patient. Neurol India. 2007;55:181-2.

5. Jhaj R Uppal R Malhotra S Bhargava VK. Cutaneous adverse reactions in-patients in a tertiary care hospital. Indian J Dermatol Venereol Leprol. 1999;65:14-7.

6. Shrivastava D Kumar A Singh SK. Adverse drug reaction monitoring in patients attending skin O.P.D at a teaching hospital. Indian J Pharmacol. 2004;36:S42.7. Devi K George S Criton S et al. Carbamazepine - the commonest cause of toxic epidermal necrolysis and Steven Johnson syndrome: A study of 7 years. Indian J Dermatol Venereol Leprol. 2005;71:325-8.

8. Sehgal S Balachandran C Shenoi SD. Clinical study of cutaneous drug reaction in 80 patients. Indian J Dermatol Venereol Leprol. 2003;69:6-7.

9. Patel RM Marfatia YS. Clinical study of cutaneous drug reaction in 200 patients. Indian J Dermatol Venereol Leprol. 2008;74:430.

10. Sharma VK Sethuraman G Kumar B. Cutaneous adverse drug reactions: Clinical pattern and causative agents- a 6 year series from Chandigarh India. J Postgrad Med.2001;47:95-9.

11. Ghosh S Acharya LD Rao PGM. Study and evaluation of the various cutaneous adverse drug reactions in Kasturba hospital Manipal. Indian J Pharm Sci. 2006;68:212- 5.

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Anesthesia for dermatologic procedures and their complications

By: Neerja Puri Ashutosh Talwar

_: Abstract Local anesthesia (anesthesia) is the reversible loss of sensation in a defined area of the body and is achieved by the topical application or injection of agents that block the generation and/or journey of nerve impulses in tissue. No dermatological procedure is possible without a local anesthetic. Local anesthesia is used in many dermatological procedures and surgical operations. The aim is to minimize pain and suffering and maximize patient comfort. This article provides an insight into the various types of anesthesia for dermatologic procedures and their complications.

Key words

Anesthesia sensation local complications dermatological procedures.

Introduction

Local anesthetics provide a reversible regional loss of sensation.1 Local anesthetics reduce pain thereby facilitating surgical procedures. Local anesthesia is required for most of the dermatologic procedures. A dermatologist has to be well-versed with all types of anesthesia whether topical anesthesia or infiltrative anesthesia. Delivery techniques broaden the clinical applicability of local anesthetics.2 These techniques include topical anesthesia infiltrative anesthesia ring blocks and peripheral nerve blocks. Regional anesthesia or field block is essentially local anesthesia but covering a larger area of subcutaneous tissue or larger peripheral nerves.3 Tumescent anesthesia is carried out by injecting large amounts of fluids containg diluted local anesthetic and adrenaline (epinephrine). It is used for liposuction and other plastic cosmetic and dermatological procedures involving large areas of skin surgery.4

Local anesthetics are relatively easy to administer and readily available.

Discussion

There are basically 2 classes of local anesthetics [Table 1] the aminoamides (amide ethers) and aminoesters (amine esters).5 Some of these are available in many different formulations including topical sprays patches ointments and injections. Duration of action depends on the agent and formulation chosen.

Lignocaine (lidocaine) is the local anaesthetic most frequently used as it is effective acts

Table 1 Different anesthetics agents and their routes of administration.

Aminoamides

Lignocaine###Spray patch ointment

(lidocaine)###injection

Bupivacaine###Injection

Mepivacaine###Injection

Prilocaine###Injection

Aminoesters###Injection

Chloroprocaine###Injection

Tetracaine

rapidly and is relatively free from toxicity and sensitivity. It is the gold standard local anesthetic by which all other anesthetics are compared. It is also the only local anesthetic available in many different formulations. Painless dermal local anesthesia can be achieved with the topical anesthetic eutectic mixture of local anesthetics (EMLA).6 This is a combination of lignocaine (lidocaine) and prilocaine and comes in the form of cream or patches.7 It is particularly useful for numbing areas that require injection especially in children. EMLA is also used in many dermatological procedures including curettage split-skin grafts and different laser techniques.8 Adrenaline (epinephrine) is sometimes added to local anesthetic formulations. It is used to:

prolong duration of anesthesia

reduce systemic absorption

reduce surgical bleeding

increase the intensity of blockade.

The following types of anesthesia are used for dermatological procedures:

I. Topical Anesthesia

Topical anesthesia refers to the modification of pain sensation or the loss of sensation caused by an agent that is applied topically to the skin. Topical anesthesia includes the administration of cryoanesthetics and the application of local anesthetic compounds which must penetrate the epidermis to have a physiologic effect.910

Because the stratum corneum is an effective barrier the delivery of anesthetics can be challenging. Recent advances in laser technology and the subsequent increase in the use of laser treatments have fueled the need for improved topical anesthetic agents and the development of such agents. CryoanestheticsCryoanesthesia refers to the external application of cold to the skin to produce numbness. Ice refrigerant sprays and liquid nitrogen have been used for this purpose. Ice applied directly to the site for 30-60 seconds provides superficial short- duration anesthesia that may be acceptable for quick shave biopsy. This application is particularly useful in children or adults who have a fear of needles. Refrigerant sprays such as ethyl chloride and dichlorotetrafluoroethane are useful for anesthetizing superficial lesions prior to their removal. These sprays are particularly helpful for anesthetizing tumors related to molluscum prior to their curettage and cysts or furuncles prior to their incision and drainage. After a frost is produced on the skin a 10- to 12-second period of anesthesia occurs before the skin temperature and sensation return to normal. As a result of this limited time frame an assistant often has to spray the area while the surgeon performs the procedure.11

Topical anestheticsTetracaine is a long-acting ester anesthetic that can be combined with epinephrine (adrenaline) and cocaine or with epinephrine and lidocaine to form mixtures known as TAC and LET respectively.12 TAC and LET are topical anesthetics used widely to anesthetize lacerations before repair. They do not induce anesthesia in intact skin; therefore their usefulness is limited. Topical lidocaine is available in a 2% or 5% concentration in a viscous or jelly formulation.13 These preparations are most effective when they are applied to mucosal surfaces. Lidocaine is also available as a 4% gel microemulsion (Tropicaine) or in a liposomal vehicle as a 4% or a 5% cream (LMX 4% and LMX 5% respectively). These preparations facilitate the diffusion through the stratum corneum providing rapid-onset anesthesia and a longer duration of action. Several studies have shown that the efficacy of these lidocaine preparations is equivalent to that of EMLA.

The recommended application time for Tropicaine and LMX is 30 minutes and occlusion is not required. The maximum area of application should not exceed 100 cm 2 in children and 600 cm in children weighing greater than 10 kg and in adults. Lidocaine iontophoresis which delivers lidocaine into the skin under the influence of an electric current has been shown to provide adequate anesthesia for venous cannulation and shave biopsies.14

EMLA cream (Astra USA Westborough Mass) is a eutectic mixture of 2.5% lidocaine and 2.5% prilocaine in an oil-in-water emulsion. This topical anesthetic cream provides adequate anesthesia for superficial curettage dermabrasion several laser procedures epilation and cryosurgery. However EMLA does not seem to be helpful in reducing the pain associated with topical photodynamic treatment of actinic keratoses. EMLA is the most widely used topical agent and has proven efficacy based on results from several clinical trials.15 EMLA cream must be applied directly to the surgical site and placed under occlusion for 1-3 hours. The anesthetic effects of EMLA may persist for as long as 2 hours. EMLA cream although safe is reported to cause systemic toxicity in children.16 In fact both CNS manifestations and methemoglobinemia are reported with the use of EMLA cream.17 Clinicians should closely adhere to the dosing guidelines listed in the Physicians' Desk Reference. They are as follows:

For infants aged 3 months or younger or those weighing less than 5 kg a maximum dose of 1 g can be applied 2 over a maximal surface area of 10 cm .

For children aged 3-12 months and weighing more than 5 kg a maximum dose of 2 g can be applied over a 2maximal surface area of 20 cm .

For children aged 1-6 years and weighing more than 10 kg a maximum dose of 10 g can be applied over a maximal surface area of 100 cm

For children aged 7-12 years a maximum dose of 20 g can be applied 2 over a maximal surface area of 200 cm .

The S-Caine Peel is a 1:1 eutectic mixture of lidocaine 7% base and tetracaine 7% base in a cream vehicle that dries to form a flexible membrane that can be easily removed. The S- Caine Peel has been shown to provide adequate anesthesia for different types of laser therapies including laser treatment of leg veins and tattoo removal. The application time is 30-60 minutes.

II. Infiltrative anesthesia

It is the most commonly used local anesthetic technique. The anesthetic agent is infiltrated directly into the surgical site by means of either intradermal injection or subcutaneous injection. Lidocaine in a 1% concentration is most commonly used for this type of infiltration.

However when increased procedure times are expected anesthetics with a longer duration of action sometimes are substituted. The infiltration of the anesthetic commonly distorts the landmarks of the site; therefore the surgical area to be anesthetized must be identified and marked prior to injection. The skin should be held taut and the tip of the needle inserted if possible into a follicular opening. This maneuver reportedly decreases the pain associated with skin perforation. The anesthetic should be infiltrated in a deep dermal location. Accentuation of the follicles or a peau d'orange appearance may be apparent if the anesthetic is injected into the upper dermis. The superficial placement of fluid is associated with greater patient discomfort. The anesthetic diffuses through the dermis with the infiltration; fortunately this effect limits the number of needle penetrations needed to anesthetize a particular site.

If additional needle sticks are needed they should be placed in an already anesthetized area.

III. Ring block or field block

A specific type of infiltration anesthesia is the ring block or field block. To perform a ring block the anesthetic agent is circumferentially injected around the surgical site without injecting the area to be excised. This infiltration prevents the nerve impulses from entering the area. A ring block is useful when the distortion of a surgical site due to the infiltration of anesthesia is not desired. Ring blocks allow a decreased volume of anesthetic to be used to anesthetize a larger area. When ring blocks are used the anesthetic should be injected into both the superficial and deep planes to be maximally effective. Ring blocks are usually given for nail avulsions.

IV. Tumescent anesthesia

This is a high volume low concentration lidocaine/epinephrine solution used by dermatologic surgeons for liposuction ambulatory phlebectomy hair transplantation laser resurfacing flaps and grafts etc.19 The solution provides anesthesia safely is practically painless to inject and markedly decreases bleeding. In 1987 Jeffery Klein a dermatologist first created the technique of tumescent anesthesia in liposuction procedures.20 Tumescent anesthesia is based on the use of dilute solutions of lidocaine (0.05-0.1%) in large volumes to provide superior anesthesia. Epinephrine (1:1000000) is added for hemostasis and the solution is buffered with sodium bicarbonate to decrease injection discomfort. Concentrations as high as 55 mg/kg have been used safely with the tumescent technique. The use of such high total doses of anesthetic without systemic toxicity is understood. The absorption kinetics of lidocaine change when high-volume low-concentration solutions are used. Decreased concentrations of lidocaine also result in slower plasma absorption with decreased peak plasma levels. The development of this anesthetic delivery system has revolutionized the surgical technique of liposuction.

The tumescent technique for local anesthesia permits regional local anesthesia of the skin and subcutaneous tissues by using direct infiltration rather than a proximal nerve block. By using large volumes of a dilute anesthetic solution consisting of lidocaine (0.1% or 0.05%) and epinephrine (1:1000000) in physiologic saline the tumescent technique produces swelling and firmness or tumescence of targeted fatty areas. The tumescent technique for liposuction is a new technique that has been developed entirely by dermatologic plastic surgeons. It is a dramatic improvement over the traditional methods that require either general anesthesia or deep intravenous (IV) sedation and narcosis. It is this author's contention that liposuction by local anesthesia is safer than liposuction by general anesthesia.

Furthermore the tumescent technique is associated with less discomfort allows a more rapid postoperative recovery and provides better aesthetic results than when liposuction is performed using other anesthetic techniques. The tumescent technique for local anesthesia permits regional local anesthesia of the skin and subcutaneous tissues by using direct infiltration rather than a proximal nerve block. By using large volumes of a dilute anesthetic solution consisting of lidocaine (0.1% or 0.05%) and epinephrine (1:1000000) in physiologic saline the tumescent technique produces swelling and firmness or tumescence of targeted fatty areas.

Recent clinical studies of the absorption pharmacokinetics of lidocaine with the tumescent technique have shown that peak plasma lidocaine levels occur approximately 12 to 15 hours after beginning the infiltration.21

This remarkably delayed absorption permits a much higher lidocaine dosage than was previously believed possible. Any reduction in a drug's rate of systemic absorption will reduce magnitude of the drug's peak plasma levels. The safe upper limit for lidocaine dosage using the tumescent technique has been estimated to be 35 mg/kg. This is approximately five times greater than standard lidocaine dosage limitations.2223

Clinical local anesthesia persists for up to 18 hours obviating the need for postoperative analgesia. The prolonged and profound anesthesia of skin and subcutaneous tissues that is provided by the tumescent technique is probably a result of exposing sufficient lengths of sensory axons to marginal blocking concentrations of lidocaine. The infiltration of a large volume of dilute epinephrine assures diffusion throughout the entire targeted area while avoiding tachycardia and hypertension. The associated vasoconstriction is so complete that there is virtually no blood loss with liposuction.24 The mechanical and pharmacologic properties of the fluid is injected subcutaneously prevent the massive shifts of intravascular fluids which are usually seen when liposuction is done by general anesthesia. With the tumescent technique there is no longer any need to replace significant volumes of IV fluids. Advantages of the tumescent technique

Minimal blood lossBlood loss with liposuction is minimized by the tumescent technique. The extensive vasoconstriction produced by large volumes of dilute epinephrine 1:1000000 produces less than12 ml of whole blood for each liter of pure fat removed by liposuction.

Prolonged local anesthesia

Clinical local anesthesia persists for up to 18 hours obviating the need for postoperative analgesia. The prolonged and profound anesthesia of skin and subcutaneous tissues that is provided by the tumescent technique is probably a result of exposing sufficient lengths of sensory axons to marginal blocking concentrations of lidocaine. The infiltration of a large volume of dilute epinephrine assures diffusion throughout the entire targeted area while avoiding tachycardia and hypertension. The associated vasoconstriction is so complete that there is virtually no blood loss with liposuction. The mechanical and pharmacologic properties of the fluid is injected subcutaneously prevent the massive shifts of intravascular fluids which are usually seen when liposuction is done by general anesthesia. With the tumescent technique there is no longer any need to replace significant volumes of IV fluids. A remarkable aspect of the tumescent technique is that there is so little postoperative discomfort.

Treated areas remain at least partially anesthetized for up to 18 hours after surgery. Thus it is not necessary to use local anesthetics that are longer acting and more cardiotoxic than lidocaine. After liposuction by the tumescent technique patients do not require postoperative analgesia.

Complications of local anesthetics Although local anesthetics are relatively safe when administered properly they have the potential to cause both regional and systemic reactions.

Local effectsLocal effects are usually a result of the injection technique. These effects include pain ecchymosis hematoma formation infection and nerve laceration. Pain is always felt when a local anesthetic is injected; however associated discomfort can be minimized by using good technique. Several factors including needle puncture of the skin tissue irritation resulting from the anesthetic and distention of tissues caused by infiltration are responsible for the discomfort associated with the use of local anesthetics. The addition of epinephrine to an anesthetic solution decreases the pH of the solution making it more acidic (pH 3.5-4.5) and leading to a more painful injection. The solution can be neutralized by the addition of sodium bicarbonate 8.4% to minimize discomfort. For example sodium bicarbonate 8.4% can be added to lidocaine with epinephrine in a 1:10 ratio to achieve a solution pH similar to that of tissue fluid (pH 7.3-7.4).

Discomfort associated with distension of the tissues during the injection of local anesthetics is caused by the rate of injection and the volume of fluid injected. To limit the pain the anesthetic should be slowly administered to allow the stretch receptors time to accommodate the new volume of fluid.25 In addition the volume of solution injected should be the smallest volume needed to achieve a loss of sensation at the surgical site. The formation of ecchymosis or a local hematoma is a result of the perforation of cutaneous blood vessels. These complications are encountered more commonly in areas of high vascularity including the mucous membranes head and genitalia. Ecchymosis and hematoma are even more pronounced when the patient has a bleeding diathesis or when the patient has been taking aspirin or other anticoagulants. If ecchymosis occurs the patient should simply be reassured. If hematoma formation occurs the patient should be evaluated.

The hematoma may require drainage with an 18-gauge needle followed by the application of a pressure dressing. Infection is an additional local complication of anesthetic use that usually occurs when proper sterile technique is not used. Cleansing the skin surface with alcohol is adequate in otherwise clean or noninfected areas.

Systemic effectsSystemic effects usually occur when blood concentrations of local anesthetic increase to toxic levels. Effects are most often encountered after the unintentional intravenous injection or administration of an excessive dose of an anesthetic. Adding a vasoconstrictor (e.g. epinephrine) can reduce the systemic absorption of an anesthetic. When using topical anesthetics strict adherence to the maximal dose or area recommended is advised; additionally great caution must be exercised when using topical anesthetics on mucosal surfaces because of the much greater absorption. Allergic reactions although systemic are not related to serum levels of the anesthetic but rather they are considered idiosyncratic and can occur at any dose. Maximal safe doses of lidocaine for local anesthesia have been determined.

For adults a maximum of 4.5 mg of lidocaine per kilogram of body weight can be administered whereas as much as 7 mg/kg can be used if the lidocaine solution has 1:100000 epinephrine added as a vasoconstrictor. For children lower maximal doses are recommended; only 1.5-2.5 mg/kg of plain lidocaine and 3-4 mg/kg of lidocaine with epinephrine should be used. Systemic toxicity resulting from excessive blood levels of nesthetics is clinically manifested as adverse reactions in the CNS and cardiovascular system.26 The CNS is affected in a predictable and dose-dependent fashion. As serum levels of lidocaine increase effects on the CNS become more severe. Any physician who uses local anesthetics must be aware of the signs and symptoms of systemic toxicity.27 At serum lidocaine levels in the range of 1-5 mcg/mL patients may complain of tinnitus lightheadedness circumoral numbness diplopia or a metallic taste in the mouth.

In addition they may complain of nausea and/or vomiting or they may become more talkative. As serum levels increase to 5-8 mcg/mL nystagmus slurred speech localized muscle twitching or fine tremors may be noticed. Patients also have been noted to have hallucinations at these levels. If blood lidocaine levels reach 8-12 mcg/mL focal seizure activity occurs; this can progress to generalized tonic-clonic seizures. Respiratory depression occurs at extremely high blood levels (20-25 mcg/mL) and can progress to coma. If signs of CNS toxicity are noted steps must be taken to reduce hypoxia and acidosis because these states increase the toxicity of local anesthetics. The patient's airway should be maintained and supplemental oxygen provided. If blood levels of carbon dioxide increase protein binding of lidocaine decreases and results in higher levels of free lidocaine in the blood.

Increased respiration and respiratory alkalosis increase the seizure threshold and decrease the uptake of the local anesthetic into the CNS. If convulsions occur the patient's airway should be maintained and supplemental oxygen administered.2829 If seizure activity is sustained 5-10 mg of diazepam should be administered slowly (1-2 mg/min) until the seizures cease. Compared with the CNS the cardiovascular system is less susceptible to the effects of local anesthetics. Most adverse effects of the cardiovascular system that occur with the administration of local anesthetics are a result of the addition of epinephrine rather than direct effects of the anesthetic. However high blood levels of local anesthetics directly reduce cardiac contractility. In addition to the direct vasodilatory effects of most local anesthetics the decrease in cardiac function can cause hypotension.

Atrioventricular blocks bradycardia and ventricular arrhythmias also are reported; these are more common in patients with known conduction disturbances and requiring antiarrhythmic medications.

Allergic reactionsAllergic reactions to local anesthetics are extremely rare especially with amide local anesthetics and account for less than 1% of the reactions caused by local anesthetics. Reactions can be type I (i.e. anaphylactic) or type IV (i.e. delayed-type hypersensitivity) reactions. These reactions are not dose related but rather they are idiosyncratic. Skin prick and intradermal test results are negative in the vast majority of patients but some authors recommend testing with the most commonly used amide local anesthetic (lidocaine). Clinical signs of type I reactions include pruritus urticaria facial swelling wheezing dyspnea cyanosis laryngeal edema nausea vomiting and abdominal cramping. Epinephrine with a concentration of 1:1000 should be subcutaneously administered at a dose of 0.3-0.5 mL. This dose can be repeated every 20-30 minutes to a maximum of 3 doses. If anaphylaxis ensues a 5-mL dose of epinephrine 1:10000 should be administered intravenously.

Type IV (i.e. delayed-type hypersensitivity) reactions account for 80% of allergic reactions to local anesthetics. They are more common with the use of topical anesthetics and may occur with anesthetics of the amide and ester subtypes. Clinical manifestations are similar to those of allergic contact dermatitis and include erythema plaques and pruritus. Patients with a history of type IV reactions are not at an increased risk of type I reactions due to amide- type anesthetics. Contact dermatitis caused by topical anesthetics should be treated with topical steroid preparations.

Conclusion

Local anesthetics are vital to cutaneous surgery. They are effective inexpensive easily accessible and relatively safe. Any surgeon using these agents should be aware of the proper technique for their use and the potential adverse effects.

References

1. Covino BG Vassallo HG eds. Local Anesthetics: Mechanisms of Action and Clinical Use. New York: Grune and Stratton; 1976. pp105-106.2. De Jong RH. Toxic effects of local anesthetics. JAMA. 1978;239:1166-8.

3. Braid DP Scott DB. The systemic absorption of local analgesic drugs. Br J Anaesth. 1965;37:394-404.

4. Amin SP Goldberg DJ. Topical anesthetics for cosmetic and laser dermatology. J Drugs Dermatol. 2005;4:455-61.5. Railan D Alster TS. Use of topical lidocaine for cosmetic dermatologic procedures. J Drugs Dermatol. 2007;6:1104-8.

6. Maunuksela EL Korpela R. Double-blind evaluation of a lignocaine-prilocaine cream (EMLA) in children. Effect on the pain associated with venous cannulation. Br J Anaesth. 1986;58:1242-5.

7. Bucalo BD Mirikitani EJ Mov RL. Comparison of skin anesthetic effect of liposomal lidocaine nonliposomal lidocaine and EMLA using 30-minute application time. Dermatol Surg. 1998;24:537-41.8. Arendt-Nielsen L Bjerring P. Laser-induced pain for evaluation of local analgesia: a comparison of topical application (EMLA) and local injection (lidocaine). Anesth Analg. 1988;67:115-23. 9. Huang W Vidimos A. Topical anesthetics in dermatology. J Am Acad Dermatol. 2000;43:286-98.10. Adriani J Dalili H. Penetration of local anesthetics through epithelial barriers. Anesth Analg. 1971;50:834-41.

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Author:Khondker, L.; Khan, M.S.I.
Publication:Journal of Pakistan Association of Dermatologists
Article Type:Report
Geographic Code:9INDI
Date:Jun 30, 2014
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