Local Cream Research Articles

Comparison of EMLA cream versus placebo in children receiving distraction therapy for venepuncture

Eutectic mixture of local anaesthetics (EMLA) cream is used routinely as a local anaesthetic prior to venepuncture in children. Despite this, however, a significant proportion of children will still be distressed. Cognitive‐behavioural interventions, such as distraction by breathing and blowing exercises, have been used and found to be helpful as alternative coping strategies. There is, however, a paucity of data regarding effectiveness. We have evaluated the efficacy of distraction therapy as a coping strategy before and during venepuncture, and in these children evaluated the need for EMLA using a prospective, randomized, double‐blind, placebo‐controlled clinical trial. Twenty‐eight children attending for venepuncture were recruited, median age 6 y (range 4–8 y), and randomly allocated to receive either EMLA or a placebo cream. All were given distraction therapy prior to and during the procedure by a play specialist. Venepuncture was carried out by one investigator. A modified pediatric pain assessment chart was used for objective pain score at the end of the procedure. After one exclusion, the treatment group (17 children) and the placebo group (10 children) were similar: median age of 6 and 7 y (range 4–8), median baseline and postprocedure heart rate and oxygen saturation. The median (interquartile range) for total pain score in the treatment group was 1 (0 to 4.5) and in the control group 1 (0 to 2.3). There was no significant difference in pain score between the two groups (Mann‐Whitney test, p= 0.7). The 95% confidence interval for the difference in pain score was 1.0 to +3.0. Conclusions: The low pain score in both groups suggests the effectiveness of distraction therapy, although factors such as skill of the operator and previous experience of the patient group are of relevance. There was no significant difference in the pain score between the EMLA and placebo groups, suggesting that in this age group if carefully selected children receive distraction during venepuncture EMLA may not be necessary.

Pediatric Regional Anesthesia: Beyond the Caudal

Pediatric Regional Anesthesia: Beyond the Caudal

REDUCTION IN PAIN ASSOCIATED WITH OPEN CARPAL TUNNEL DECOMPRESSION

Patients treated by open carpal tunnel decompression under local anaesthetic experience significant pain with the introduction of local anaesthetic before operation. A prospective double-blind randomized placebo controlled trial was carried out to assess whether this pain could be reduced with the pre-application of a topical lignocaine-prilocaine anaesthetic cream. Nineteen patients undergoing simultaneous bilateral operations were studied. Pain, measured with a visual analogue scale, was significantly reduced on the sides treated with anaesthetic cream. On a four point verbal scale the rating on the placebo side was “moderate” or “severe”, compared to “mild” on the anaesthetic cream side. The reduction in pain was greater in women, possibly due to a relatively thinner dermis. There were no adverse effects.

The use of EMLA reduces the pain associated with digital ring block for ingrowing toenail correction

Treatment of ingrowing toenail is commonly performed under local anaesthesia with a digital ring block. Ring block can be associated with significant pain, caused by needle insertion and deposition of the local anaesthetic agent. EMLA, a topical anaesthetic cream, is widely used to alleviate the pain of venepuncture. The aim of this study was to investigate whether the discomfort of digital block could be reduced by prior application of EMLA. Fifty-five patients who were scheduled for ingrowing toenail under local anaesthesia were randomized into two groups. In Group 1 (n = 30), EMLA was applied around the base of the affected hallux for at least 1 h before ring block. In Group 2 (n = 25), a placebo cream was used. In this double-blind study, patients assessed the pain caused by a standardized ring block using 100-mm visual analogue pain score. The mean visual analogue pain score in Group 1 was 28.1 and 50.1 in Group 2 (P < 0.0001). We conclude that EMLA significantly reduces the pain associated with digital ring block.

The use of EMLA reduces the pain associated with digital ring block for ingrowing toenail correction

Treatment of ingrowing toenail is commonly performed under local anaesthesia with a digital ring block. Ring block can be associated with significant pain, caused by needle insertion and deposition of the local anaesthetic agent. EMLA, a topical anaesthetic cream, is widely used to alleviate the pain of venepuncture. The aim of this study was to investigate whether the discomfort of digital block could be reduced by prior application of EMLA. Fifty-five patients who were scheduled for ingrowing toenail under local anaesthesia were randomized into two groups. In Group 1 (n = 30), EMLA was applied around the base of the affected hallux for at least 1 h before ring block. In Group 2 (n = 25), a placebo cream was used. In this double-blind study, patients assessed the pain caused by a standardized ring block using 100-mm visual analogue pain score. The mean visual analogue pain score in Group 1 was 28.1 and 50.1 in Group 2 (P < 0.0001). We conclude that EMLA significantly reduces the pain associated with digital ring block.

Drug trials in children: problems and the way forward.

The drug-licensing system was introduced with the Medicines Act of 1968, following the thalidomide disaster, with the aim of ensuring that medicines are safe, effective and of high quality. There is increasing concern from the pharmaceutical industry, paediatricians, paediatric pharmacists and the Government that many medicines routinely used in children have not been formally evaluated by this system. Such use is therefore not supported by the assurances that the process brings. A joint report was produced in 1996 by the British Paediatric Association (now the Royal College of Paediatrics and Child Health) and the Association of the British Pharmaceutical Industry. This described in detail the current unsatisfactory situation and made specific recommendations for a way forward [1]. Since then several studies have documented the extent of unlicensed and off-label drug use in critically ill children, paediatric medical and surgical inpatients and neonates [2–4]. These studies all show that unlicensed and off-label drug use is a frequent occurrence for children in hospital with up to 90% of newborn infants in intensive care receiving either unlicensed or off-label treatment. Unlicensed medicines may be those compounded in a hospital pharmacy department or by a ‘specials’ manufacturer due to a lack of licensed alternatives. These medicines may not necessarily undergo the rigorous quality testing procedures that a licensed preparation must, and their quality may be variable. The term off-label refers to the use of a medicine outside the specifications of the product licence [5]. This covers medicines used at a different dosage to that recommended, in different age groups, by a different route or for a different indication. These off-label uses may be based on reliable published data, in which case prescribers can feel confident in using medicines in an off-label manner since this practice would be supported by peer review. In other instances they may rely more on the experience of the paediatrician or pharmacist, or drug information resources such as those of DIAL (Drug Information Advisory Line, Alder Hey Children’s Hospital, Liverpool). They are less likely to be supported by extensive clinical trial information, as would the manufacturer’s recommended uses of a licensed preparation.

A randomized, controlled trial of a eutectic mixture of local anesthetic cream (lidocaine and prilocaine) versus penile nerve block for pain relief during circumcision

Objective: We set out to compare a eutectic mixture of local anesthetic cream (lidocaine and prilocaine) to dorsal penile nerve block with lidocaine for anesthesia during circumcision. Study Design: In a double-blind study, term newborns were randomized to local anesthetic cream and sodium chloride solution dorsal penile nerve block (n = 31) or to placebo cream and lidocaine dorsal penile nerve block (n = 29). Pain was assessed by determination of heart rate, respiratory rate, and behavioral distress scoring. Group differences were evaluated with repeat-measures analyses of variance. Results: Distress scores and heart rates were significantly higher in the eutectic mixture group than in the lidocaine group. Respiratory rates were higher in the eutectic mixture group but did not reach statistical significance. Conclusions: Distress scores and heart rates were significantly higher in infants treated with the anesthetic mixture than in infants treated with lidocaine. Dorsal penile nerve block with lidocaine is a more efficacious means of providing anesthesia for neonatal circumcision than the mixture of local anesthetics. (Am J Obstet Gynecol 1999;181:1506-11.)

Insertion of long lines in the pediatric emergency department.

The purpose of this study was: 1) to evaluate the role of the pediatric emergency department (PED) in placing peripherally inserted midline or central catheters (long lines), and 2) to review indications and complications to use this technology to reduce the number and duration of admissions and provide an alternative method for administering intravenous therapy. Retrospective chart review of all patients taken from a procedure log who had long lines placed in the emergency department of a children's hospital. Twenty-eight patients had 30 long line insertions over a 36-month period. Fourteen were female; age ranged from 1 to 36 years with a median of 9 and a mean of 11.1 +/- 8.4. The indication for insertion was for parenteral antibiotics in 27 of 28 (96%) patients and for parenteral nutrition in 1 (4%) patient. The catheters varied in length from 8 to 60 cm. Twelve of 30 (40%) catheters terminated centrally in the subclavian or superior vena cava, while 18 (60%) were in the peripheral cephalic, basilic, or axillary veins. Chest radiography confirmed positioning in 12 of 12 inserted centrally and in 15 of 18 (83%) in the peripheral circulation. Half of the patients received no premedication for the procedure; 10 (33%) received topical anesthetic cream; 2 (7%) local infiltration of anesthetic, and 2 (7%) parenteral sedation. Twenty-one of 30 (70%) patients were discharged directly from the emergency department; 3 (10%) were discharged after admission to the hospital to complete treatment at home with their long lines, and 6 (20%) used their long lines for in-hospital therapy only. Eight of 30 (27%) placements were for patients specifically referred to the PED for placement or replacement of a long line. Twelve of 30 (40%) lines were placed in children presenting for intravenous therapy for cellulitis. These patients received a long line with home i.v. therapy instead of the traditional admission. The duration of intravenous treatment documented for all patients ranged from 1 to 62 days with a median of 10.5, and a mean of 16.2 +/- 17.8, compared with the duration of the line ranging from 1 to 28 days with a median of 4, and a mean of 7.3 +/- 8.0. Ten of 30 (33%) had their line for 3 days or less. The short duration was due to problems with line function in 5 of 10, and intentional removal secondary to improved cellulitis in 5. There were no significant complications with the lines reported during placement or while in use; however, 8 of 30 (27%) of the lines placed developed problems with function, requiring repair or replacement. 1) Long lines can be inserted in the pediatric emergency department by physicians with different levels of training with minor complications and no adverse clinical effects; 2) the placement of long lines can eliminate the need for hospitalization in some cases, reduce the duration of hospitalization in others, and lessen the need for repeated venipunctures for routine peripheral catheter replacement in patients requiring i.v. therapy; 3) the planned duration of therapy as well as other factors not analyzed in this study should be considered when selecting patients for long line placement in the emergency department.

Noradrenaline provokes axon reflex hyperaemia in the skin of the human forearm

High doses of noradrenaline increase the sensitivity of skin to heat, presumably by sensitizing nociceptive afferent fibres. Since activation of these fibres increases local blood flow by an axon reflex mechanism, noradrenaline might simultaneously evoke adrenoceptor-mediated vasoconstriction and axon reflex vasodilatation. To investigate this possibility, noradrenaline was introduced into the skin of the human forearm by iontophoresis, and changes in blood flow were monitored in nearby skin. Increases in blood flow were greater near the site of noradrenaline iontophoresis than near the site of saline iontophoresis. Since the response was limited in its distribution to a few centimeters from the site of iontophoresis, hyperaemia was most likely due to a local mechanism rather than a spinal or supraspinal reflex. In addition, pretreatment of the skin with a local anaesthetic cream inhibited the increase in flow, indicating that the response was mediated neurally. These findings suggest that activation of nociceptive afferents by noradrenaline provokes axon reflex hyperaemia.

Effects of amide local anaesthetics on eicosanoid formation in burned skin.

Previous studies have demonstrated potent inhibition of burn oedema and progressive ischaemia by local anaesthetics. Since eicosanoids have been suggested to play an important role in the pathophysiology of burns, we compared in the present ex vivo study the effects of topical lidocaine/prilocaine cream (EMLA, ASTRA, Sweden) and intravenous lidocaine with that of saline on eicosanoid formation by normal and burned rat skin. A full-thickness burn trauma was induced in the abdominal skin. All the agents were given 5 min postburn until 2 h after the trauma. The experimental skin was subsequently removed and incubated in Krebs solution for 1 h. Eicosanoid concentrations in the solution were analysed by radioimmunoassay. EMLA cream induced a significant inhibition of TXB2 (P<0.05) and 6-Keto-PGF1alpha (P<0.01) but not of PGE release from burned skin as compared to saline treatment. Intravenous lidocaine infusions did not significantly influence the release of any of the measured eicosanoids versus saline. In conclusion, the lack of effect of intravenous lidocaine could relate to the severe burn trauma inducing rapid ischaemia which may have interfered with the delivery of the agent to the burned tissues or to insufficient concentrations achieved in the burn area. Topical treatment of burned skin with a local anaesthetic cream significantly reduced the release of TXB2 and 6-Keto-PGF1alpha, suggesting a possible mechanism of action in progressive burn ischaemia.

Effects of single and repeated applications of a eutectic mixture of local anaesthetics (EMLA ®) cream on spontaneous and evoked pain in post-herpetic neuralgia

The analgesic effects of single and repeated applications of a eutectic mixture of local anaesthetics (EMLA) cream on both spontaneous and evoked pains were evaluated in 11 patients with post-herpetic neuralgia (PHN). Detection thresholds, pain thresholds and the responses to suprathreshold mechanical and thermal stimuli were quantitatively determined at baseline, 30 min after the first application and after a series of daily applications over six consecutive days (duration of application: 5 h/day). In the acute situation, EMLA produced an overall anaesthetic effect without significantly reducing spontaneous ongoing pain and mechanical allodynia. Repeated applications significantly reduced paroxysmal pain and both the dynamic and static subtypes of mechanical hyperalgesia. The effects on spontaneous ongoing pain were more variable. They were inversely correlated to the magnitude of the thermal deficit at baseline, and were significant only in patients with dynamic mechano-allodynia. Pathophysiological implications of these results are discussed.

STINGING INSECT HYPERSENSITIVITY: A PRACTICE PARAMETER

STINGING INSECT HYPERSENSITIVITY: A PRACTICE PARAMETER

Pressure pain thresholds in different tissues in one body region. The influence of skin sensitivity in pressure algometry.

This study aimed at determining whether there are differences in pressure pain sensitivity in different tissues in the same body region when systematically assessed, before and after skin hypoesthesia. Pressure pain thresholds (PPTs) were assessed bilaterally in 15 healthy females at the bony part of the epicondylus lateralis humeri, at the belly of m. extensor carpi ulnaris and at m. brachioradialis where the superficial radial nerve branches pass underneath ("muscle/nerve" site). Following a double blind design, a local anaesthetic cream (EMLA) or a control cream was applied to the skin and PPTs were reassessed. The PPT was significantly (p < 0.001) lower at the "muscle/nerve" site than at the bony and "pure" muscle sites. The PPTs over the bony and "pure" muscle sites did not differ. There was no significant difference when PPTs were compared before and after application of EMLA cream. However, PPTs after control cream were lower (p < 0.001) over all examined areas than those obtained prior to cream application. Thus, EMLA cream increased PPTs compared to control sites in all examined areas (p < 0.001). Under the given circumstances, skin pressure pain sensitivity was demonstrated to influence the PPT.

Vulvar vestibulitis treated by modified vestibulectomy

Objective: A prospective study to evaluate the success of a modified vestibulectomy in treating vulvar vestibulitis. Methods: Fifty seven consecutive women with vulvar vestibulitis and suitable for surgery based on the criteria: superficial dyspareunia, erythematous vestibular region, positive Q-tip test, symptoms reduced with local anesthetic cream. A modified vestibulectomy with or without a modified Fentons procedure was performed. Response was based on return to normal coitus, 3 months after surgery. Results: Most women suffered from chronic conditions (median duration of symptoms=18 months). The median age was 28 years (range 18–53). Any infections were treated prior to surgery. All but 4 (7%) had histological abnormalities, mainly non-specific inflammation. In 18% of women who had cervical cytology some abnormality was detected. Mean follow-up time was 12 months (range 2–42). Three women were not evaluable. Complete response to surgery was achieved in 33 (61.1%) of the women, partial response was achieved in 15 (27.8%). Six (11.1%) had persistent symptoms, four of whom has psychosexual problems. Conclusion: Presently, surgery remains the most successful intervention for vulvar vestibulitis. Modified surgery which is less destructive seems to afford acceptable results. The completion of randomized studies are needed to recognise the optimum surgical procedure.

A randomized, placebo-controlled comparison of EMLA ™ and dorsal penile nerve block for pain relief during neonatal circumcision

Objective: To evaluate the relative efficacies of eutetic mixture of local anesthetics (EMLA ™) cream and dorsal penile nerve block (DPNB) for pain relief during neonatal circumcision. Methods: After parental informed consent, appropriate-for-gestational age, term, healthy newborns were randomized to receive either EMLA cream and placebo saline DPNB or placebo cream and 1% lidocaine DPNB. Placebo and EMLA cream were prepared by the pharmacy and applied by study nurses. Preloaded syringes of saline or 1% lidocaine were also prepared by the pharmacy for the DPNB injections. This ensured blinding of the surgeons and assistants at the time of circumcisions. Circumcisions were performed with the Gomco clamp technique by one of three obstetrics and gynecology residents. Pain levels were assessed by measuring pulse and respiratory rates and determining Brazelton states at each step of the circumcision. Videotapes were made of each procedure to allow later scoring by a single blinded observer for Brazelton states. Brazelton state scores increase with increased infant pain and distress, as do heart and respiratory rates. Means were compared by t test and proportions by χ 2. A P value of .05 was considered statistically significant. Results: A total of 60 infants were randomized, 29 to DPNB and 31 to EMLA. Preoperative Brazelton state scores, heart rates, and respiratory rates were similar in both groups. Brazelton state scores were lower in the DPNB group at each step of the procedure—injection, dissection of the foreskin, clamp placement, and clamp removal—and postoperatively and overall, but the differences only reached statistical significance during dissection and clamp removal. Heart and respiratory rates also were lower at all surgical steps in the DPNB group but only reached statistical significance during postoperative observation. Conclusions: Although both EMLA and DPNB have been shown in other studies to decrease pain during neonatal circumcisions, DPNB has greater effectiveness in relieving the pain of circumcision.

Special characteristics of topical treatment in childhood

Although the barrier function and thickness of the stratum corneum is fully developed in newborns, the infant shows numerous differences in cutaneous and systemic metabolism of topically applied substances in comparison to adults. This discrepancy between children and adults has been explained by the greater systemic availability due to the greater surface area to weight ratio in children. Several topically applied drugs such as hexachlorophene, phenol, salicylic acid and boric acid in high concentration or on large areas have caused toxic reactions and fatalities in infants. Therapeutic approaches to childhood dermatoses differ from these used in adults. These age-dependent differences concerning the topical application of glucocorticosteroids, urea and dyes are described for the treatment of atopic eczema. The development of innovative topical drugs may extend therapeutic options especially in children as shown by a new topical anesthetic cream improving the treatment of mollusca contagiosa, a common childhood problem. Finally, certain physiological differences should be considered in newborn and infant skin care.

Prolonged contact with topical anaesthetic cream: A case report

Prolonged contact with topical anaesthetic cream: A case report

NEONATAL CIRCUMCISION AND PAIN RESPONSE DURING ROUTINE 4 TO 6 MONTH VACCINATION. • 1070

Background: There are preliminary data to suggest that pain experienced in the neonatal period may have long-lasting effects on the infant. The objectives of this study were to determine whether circumcised infants differ in their pain response at 4 or 6 month vaccination compared to uncircumcised infants, and if vaccination response is affected by pre-treatment of circumcision pain with the topical anesthetic cream EMLA.

Ocular toxicity following topical application of anesthetic cream to the eyelid skin

Background and objective The use of topical anesthetic cream in the periorbital region may be of clinical value. The potential for toxic effects from such use has not been studied in a controlled manner. This study was performed to evaluate the potential ocular toxicity of anesthetic cream topically applied to the eyelid in an animal model. Materials and methods Ten rabbits underwent periorbital eutectic mixture of local anesthetics (EMLA) (2.5 percent lidocaine and 2.5 percent prilocaine) application and were observed for evidence of gross or microscopic ocular toxicity. Baseline external and anterior segment examinations were performed, including biomicroscopy and fluorescein staining, after which a standard quantity of EMLA cream (0.75 g) was applied along the upper eyelid and covered with an occlusive dressing. After 1 hour of treatment, the eyelid and anterior segment were examined for evidence of adverse reaction. The eyelids were excised and examined histopathologically. Results No significant adverse effects were noted on external lid and anterior segment examination. The histopathologic findings were within normal limits. Conclusions This study suggests that external application of EMLA cream to the eyelid does not induce local toxicity in the rabbit model. The external application of EMLA cream may be safe in the periorbital region.

Methemoglobinemia From Perineal Application of an Anesthetic Cream

A 34-year-old woman presented with cyanosis and a methemoglobin level of 23.2% after perineal application of a topical anesthetic cream containing 20% benzocaine. Many commonly used products contain high levels of benzocaine, and their use can lead to life-threatening methemoglobin levels. This case reinforces the need for stricter guidelines for product use and warning labels to alert consumers to this potential side effect of topical benzocaine-containing products sold over the counter. [Ferraro-Borgida MJ, Mulhern SA, DeMeo MO, Bayer MJ: Methemoglobinemia from perineal application of an anesthetic cream. Ann Emerg Med June 1996;27:785-788.]