Percutaneous penetration kinetics of lidocaine and prilocaine in two local anesthetic formulations assessed by in vivo microdialysis in pigs.

Biol Pharm Bull. 2007 Apr;30(4):830-4

Authors: Wei H, Chen Y, Xu L, Zheng J

The aim of this study was to characterize and compare the percutaneous penetration kinetics of lidocaine (L) and prilocaine (P) in two local anesthetic formulations by in vivo microdialysis coupled with HPLC. The microdialysis system for studying lidocaine and prilocaine was calibrated by a no-net-flux method in vitro and retrodialysis method in vivo, respectively. A dosage of 0.2 g/cm2 of an in-house P-L formulation (2.5% lidocaine and 2.5% prilocaine, methylcellulose-based) and commercially available Eutectic Mixture of Local Anesthesia (EMLA, 2.5% lidocaine and 2.5% prilocaine, carbopol-based) was separately but symmetrically applied in the dorsal region of pigs. Saline (0.9%, w/v) was perfused into the linear microdialysis probe at a flow rate of 1.5 microl/min. Dialysate was collected upon topical application up to 6 h at 20-min intervals and assessed by HPLC. The results demonstrated the area under the concentration-time curve (AUC(0-6 h)) of lidocaine and prilocaine in EMLA was 71.95+/-23.36 microg h/ml and 38.01+/-14.8 microg h/ml, respectively, in comparison to 167.11+/-56.12 microg h/ml and 87.02+/-30.38 microg h/ml in the P-L formulation. The maximal concentrations (Cmax) of lidocaine and prilocaine in the dermis were 29.2+/-9.08 microg/ml and 16.54+/-5.31 microg/ml in EMLA and 80.93+/-17.98 microg/ml and 43.69+/-12.87 microg/ml in the P-L formulation, respectively. This study indicates a well-calibrated microdialysis system can provide vital real-time information on percutaneous drug delivery and specifically a methylcellulose-based P-L formulation can increase percutaneous absorption of both lidocaine and prilocaine in pigs compared to carbopol-based EMLA.

PMID: 17409532 [PubMed - indexed for MEDLINE]

Evaluation of three topical anaesthetic agents against pain: a clinical study.

Indian J Dent Res. 2006 Oct-Dec;17(4):155-60

Authors: Nayak R, Sudha P

AIM: To compare pain responses of children during local anaesthetic infiltration at bilateral buccal sites prepared with topical application of EMLA 5% cream, benzocaine 18% gel or lignocaine 5% ointment and also to find out the rapidity of onset of action of these agents. METHODS: 60 healthy children aged 6 to 12 years old, received bilateral buccal infiltration following application of topical anaesthetic agents applied in a double blind design. Pain responses were compared based on subject self report using visual analogue scale (VAS) and operator assessment using Sound -Eye -Motor (SEM) scale. RESULTS: Benzocaine gel had the rapidest onset of action. EMLA 5% cream proved to be superior in pain reduction compared to benzocaine and lignocaine. Taste acceptance was better with benzocaine gel. Further studies are required for EMLA cream with an improved formulation more suitable for mucosal application before its routine use in dentistry.

PMID: 17217210 [PubMed - indexed for MEDLINE]

A comparison of a needle-free injection system for local anesthesia versus EMLA for intravenous catheter insertion in the pediatric patient.

Anesth Analg. 2006 Feb;102(2):411-4

Authors: Jimenez N, Bradford H, Seidel KD, Sousa M, Lynn AM

Placement of IV catheters is a painful and stressful procedure for children. J-Tip is a needle-less Food and Drug Administration approved injection system that can be used for delivery of local anesthetic before IV cannulation. In this study, we compared the effectiveness of J-Tip versus eutectic mixture of local anesthetics (EMLA) to facilitate IV cannulation and provide adequate analgesia before IV placement. Children 7-19 years of age (n = 116) were randomized to receive 0.25 mL of 1% buffered lidocaine with J-Tip (n = 57) or 2.5 g of EMLA (n = 59) before IV cannulation. Measurements of success of cannulation (number of attempts for IV placement) and pain (0-10 visual analog scale) at application of local anesthetic and at cannulation were performed. There was a significant (P = 0.0001) difference in pain ratings during IV cannulation between EMLA (median = 3) and the J-Tip (median = 0). Eighty-four percent of patients reported no pain at the time of J-Tip lidocaine application compared to 61% in the EMLA group at the time of dressing removal (P = 0.004). We did not find differences in the number of attempts for IV cannulation. J-Tip application of 1% buffered lidocaine before IV cannulation is not painful and has better anesthetic effectiveness compared with EMLA.

PMID: 16428534 [PubMed - indexed for MEDLINE]

Rapid skin anesthesia using a new topical amethocaine formulation: a preclinical study.

Anesth Analg. 2004 May;98(5):1407-12, table of contents

Authors: Arévalo MI, Escribano E, Calpena A, Domenech J, Queralt J

We developed a fast-acting topical amethocaine emulsion and tested its analgesic activity against heat or mechanically induced pain in a rat paw model. The first experiment was performed in rats made hyperalgesic or allodynic after carrageenan-induced inflammation. Rats were distributed in five subgroups, each receiving topically one of the following: amethocaine microemulsion, amethocaine gel (Ametopgel), EMLA (Eutectic Mixture of Local Anesthetics) cream, amethocaine infiltration, or nothing (controls). The second experiment was conducted on healthy, selected heat- or touch-hypersensitive rats, which were distributed as in the first experiment. Paw withdrawal time from a heat and a mechanical stimulus was used as a pain index. In the first experiment, antihyperalgesic activity appeared at 4.2, 13.8, and 14 min after amethocaine microemulsion, gel, or EMLA cream, respectively. Amethocaine microemulsion was the only topical formulation with an antiallodynic effects, although less than with amethocaine infiltration. In healthy rats (second experiment), all topical formulations produced similar analgesic effects in heat-induced pain of the ipsilateral paw. Activity in the contralateral paw appeared earlier with amethocaine microemulsion, which was also the only one that increased touch-induced withdrawal time in the ipsi- and contralateral paws. Therefore, the microemulsion could be valuable for improving amethocaine skin penetration and thus bringing rapid pain relief. IMPLICATIONS: Topical anesthetics are used in several painful clinical procedures, but they tend to have a slow onset time. A new amethocaine microemulsion with a faster onset of analgesia than commercial formulations was developed and its activity tested in pain states induced by heat or mechanical stimulus in inflamed and healthy rat paws.

PMID: 15105222 [PubMed - indexed for MEDLINE]

Topical anaesthesia in neonates, infants and children.

Br J Anaesth. 2004 Mar;92(3):450; author reply 450-1

Authors: Lillieborg S, Otterbom I, Ahlen K

PMID: 14970141 [PubMed - indexed for MEDLINE]

A randomized trial of eutectic mixture of local anesthetics during lumbar puncture in newborns.

Arch Pediatr Adolesc Med. 2003 Nov;157(11):1065-70

Authors: Kaur G, Gupta P, Kumar A

OBJECTIVE: To determine the efficacy of a topical anesthetic cream, eutectic mixture of local anesthetics (EMLA), in alleviating pain associated with lumbar puncture in newborns. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Neonatal intensive care unit of a university teaching hospital.Patients Sixty consecutive newborns (gestational age, >or=34 weeks) undergoing diagnostic lumbar puncture.Intervention Topical application of 1 g of EMLA or placebo 60 to 90 minutes before lumbar puncture. MAIN OUTCOME MEASURES: Heart rate, transcutaneous oxygen saturation level, and total behavioral score recorded on a video camera and graded according to the Neonatal Facial Coding System. RESULTS: Compared with baseline, all newborns experienced pain as evidenced by increased heart rate, decreased oxygen saturation level, and total behavioral score (all within-groups differences were significant using repeated-measures analysis of variance; P<.001) during the procedure. Compared with placebo, EMLA significantly attenuated the pain response as shown by a lower mean +/- SE heart rate (per minute), particularly at needle insertion (EMLA: 159.3 +/- 2.3; placebo: 175.2 +/- 2.7; P<.001) and needle withdrawal (EMLA: 153.8 +/- 2.6; placebo: 167.3 +/- 2.5; P<.001), and a lower mean +/- SE total behavioral score, again at insertion (EMLA: 4.0 +/- 0.3; placebo: 5.0 +/- 0.0; P =.004) and withdrawal (EMLA: 1.8 +/- 0.3; placebo: 3.9 +/- 0.3; P<.001). There was no statistically significant difference between groups with regard to oxygen saturation level. CONCLUSIONS: Lumbar puncture in newborns produces pain responses. Eutectic mixture of local anesthetics is an efficacious agent for reducing the pain associated with needle insertion and withdrawal during lumbar puncture in newborns.

PMID: 14609894 [PubMed - indexed for MEDLINE]

Full-face laser resurfacing using a supplemented topical anesthesia protocol.

Arch Dermatol. 2003 Oct;139(10):1279-83

Authors: Kilmer SL, Chotzen V, Zelickson BD, McClaren M, Silva S, Calkin J, No D

BACKGROUND: Laser resurfacing has become a popular modality for the treatment of photodamaged skin, rhytids, and acne scarring. In many cases, this procedure is performed under general anesthesia or intravenous sedation in conjunction with nerve blocks and local infiltration. OBJECTIVE: To evaluate the safety and efficacy of facial carbon dioxide laser resurfacing using a supplemented topical anesthesia protocol. DESIGN: Nonrandomized case series of patients observed for 1 year. SETTING: Outpatient surgery center. PATIENTS: Two hundred consecutive patients undergoing treatment for facial rhytids or acne scarring.Intervention Full-face carbon dioxide laser resurfacing procedures were performed using a supplemented topical anesthesia protocol. Pretreatment medications included diazepam, oral analgesics, and intramuscular ketorolac tromethamine. MAIN OUTCOME MEASURES: Tolerability of procedure, healing times, and adverse effects. RESULTS: Topical anesthesia provided effective and sufficient anesthesia in most cases. Only 10 of 200 patients required additional anesthesia (regional nerve blocks and/or local infiltration). Substantial improvement of rhytids, photodamage, and acne scarring was observed. Posttreatment hypopigmentation was seen in 1 patient. Scarring was not observed.Conclusion A supplemented topical anesthesia protocol for full-face laser resurfacing is a safe and effective alternative to traditional anesthesia strategies.

PMID: 14568831 [PubMed - indexed for MEDLINE]

Piroxicam gel, compared to EMLA cream is associated with less pain after venous cannulation in volunteers.

Can J Anaesth. 2003 Oct;50(8):775-8

Authors: Dutta A, Puri GD, Wig J

PURPOSE: To evaluate and compare the analgesic efficacy and anti-inflammatory effects of topical piroxicam gel vs eutectic mixture of local anesthetic (EMLA) cream applied to the peripheral venous cannulation site in adult volunteers. METHODS: Piroxicam gel and EMLA cream were randomly applied on the dorsum of the right and left hand of ten volunteers who acted as their own control. A venous cannula was inserted (no iv infusion) and removed after one hour. Pain scores and signs of inflammation were noted at the cannulation site up to 48 hr. RESULTS: Pain scores with piroxicam gel were higher on cannulation and on advancement of the cannula (P < 0.05). Thereafter, pain scores were significantly higher with EMLA (P < 0.05). Blanching was present at all the peripheral venous sites treated with EMLA cream. Signs of inflammation (erythema, edema) were not more frequent with EMLA than with piroxicam (P > 0.05). Induration was more frequent with EMLA at six hours. CONCLUSION: In volunteers EMLA cream is associated with less pain on cannulation and cannula advancement compared to piroxicam gel. Topical application of piroxicam gel before peripheral venous cannulation alleviates pain and, possibly, inflammation in the period subsequent to cannulation itself.

PMID: 14525815 [PubMed - indexed for MEDLINE]

Statistical process control methods allow the analysis and improvement of anesthesia care.

Can J Anaesth. 2003 Oct;50(8):767-74

Authors: Fasting S, Gisvold SE

PURPOSE: Quality aspects of the anesthetic process are reflected in the rate of intraoperative adverse events. The purpose of this report is to illustrate how the quality of the anesthesia process can be analyzed using statistical process control methods, and exemplify how this analysis can be used for quality improvement. METHODS: We prospectively recorded anesthesia-related data from all anesthetics for five years. The data included intraoperative adverse events, which were graded into four levels, according to severity. We selected four adverse events, representing important quality and safety aspects, for statistical process control analysis. These were: inadequate regional anesthesia, difficult emergence from general anesthesia, intubation difficulties and drug errors. We analyzed the underlying process using 'p-charts' for statistical process control. RESULTS: In 65,170 anesthetics we recorded adverse events in 18.3%; mostly of lesser severity. Control charts were used to define statistically the predictable normal variation in problem rate, and then used as a basis for analysis of the selected problems with the following results: Inadequate plexus anesthesia: stable process, but unacceptably high failure rate; Difficult emergence: unstable process, because of quality improvement efforts; Intubation difficulties: stable process, rate acceptable; Medication errors: methodology not suited because of low rate of errors. CONCLUSION: By applying statistical process control methods to the analysis of adverse events, we have exemplified how this allows us to determine if a process is stable, whether an intervention is required, and if quality improvement efforts have the desired effect.

PMID: 14525814 [PubMed - indexed for MEDLINE]

The efficacy of 5% lidocaine-prilocaine (EMLA) cream on pain during intravenous injection of propofol.

Anesth Analg. 2003 Sep;97(3):713-4

Authors: McCluskey A, Currer BA, Sayeed I

Topical anesthesia using 60% lidocaine tape reduces the incidence of propofol injection pain. We conducted a randomized prospective double-blinded placebo-controlled study to assess the analgesic efficacy of pretreatment with topical 5% lidocaine-prilocaine (EMLA) cream in 90 ASA physical status I and II adult patients scheduled to undergo day-case gynecological surgery. Propofol injection pain was not reduced by pretreatment with EMLA cream, whereas the addition of lidocaine to propofol did significantly reduce propofol injection pain compared with the control group (P = 0.002). We conclude that topical anesthesia with EMLA cream applied for 60 min does not significantly reduce propofol injection pain.

PMID: 12933391 [PubMed - indexed for MEDLINE]

EMLA cream versus dorsal penile nerve block for postcircumcision analgesia in children.

Anesth Analg. 2003 Feb;96(2):396-9, table of contents

Authors: Choi WY, Irwin MG, Hui TW, Lim HH, Chan KL

We conducted a prospective, randomized, double-blinded trial comparing preoperative application of EMLA cream and sodium chloride solution dorsal penile block (n = 31) with placebo cream and bupivacaine dorsal penile nerve block (n = 32) for postcircumcision analgesia. Pain was assessed using modified Children's Hospital of Eastern Ontario Pain Scale and the duration of block by the time to requirement of first dose of postoperative analgesic. There was no difference in Children's Hospital of Eastern Ontario Pain Scale between the two groups, but bupivacaine dorsal penile nerve block resulted in longer analgesia (P = 0.003). There were no local or systemic complications related to either technique, and there was a very small incidence of vomiting. We conclude that preoperative application of EMLA cream is an effective and simple method to produce postcircumcision analgesia with a very small incidence of adverse effects.

PMID: 12538184 [PubMed - indexed for MEDLINE]

Topical anesthetics for intravenous insertion in children: a randomized equivalency study.

Pediatrics. 2002 Oct;110(4):758-61

Authors: Kleiber C, Sorenson M, Whiteside K, Gronstal BA, Tannous R

OBJECTIVES: Children view needle sticks as the worst source of pain and fear in the hospital setting. In an effort to minimize the pain of needle sticks, the use of eutectic mixture of lidocaine and prilocaine (EMLA) has become standard practice in many children's hospitals. Unfortunately, EMLA requires at least 60 minutes to be fully effective and reportedly may cause vasoconstriction, leading to difficult vein cannulation. A newly available local anesthetic (ELA-Max) may require less time and cause less vasoconstriction. The purpose of this randomized crossover study was to investigate the anesthetic equivalence of EMLA and ELA-Max. METHODS: Thirty well children (14 girls and 16 boys) who were between the ages of 7 and 13 years volunteered to have EMLA applied to the dorsal aspect of 1 hand for 60 minutes and ELA-Max applied to the other hand for 30 minutes. Right and left hands were randomized to treatment type and order of intravenous (IV) insertion. Clinical Research Center nurses, blind to the anesthetic randomization, attempted to insert a 22-gauge Teflon IV catheter into a vein in each hand. The children rated pain during IV insertion on the Oucher scale, and the nurse rated the difficulty of the insertion. RESULTS: There was no significant difference in pain ratings for hands that were treated with EMLA (mean: 20.5) or with ELA-Max (mean: 24), and there was no difference for the difficulty of vein cannulation. Children's preprocedure state anxiety was positively associated with pain ratings. CONCLUSIONS: ELA-Max, applied for 30 minutes before IV cannulation, has an anesthetic effectiveness similar to EMLA applied for 60 minutes. Some children rated IV insertion pain fairly high for both hands (eg, 60 on a 0- to 100-point scale) despite anesthetic treatment. Preprocedural anxiety may affect the perception and/or rating of pain. There were no differences between hands that were treated with EMLA or with ELA-Max for success of IV insertion.

PMID: 12359791 [PubMed - indexed for MEDLINE]

Principles of office anesthesia: part II. Topical anesthesia.

Am Fam Physician. 2002 Jul 1;66(1):99-102

Authors: Kundu S, Achar S

The development of topical anesthetics has provided the family physician with multiple options in anesthetizing open and intact skin. The combination of tetracaine, adrenaline (epinephrine), and cocaine, better known as TAC, was the first topical agent available for analgesia of lacerations to the face and scalp. Cocaine has been replaced with lidocaine in a newer formulation called LET (lidocaine, epinephrine, and tetracaine). For analgesia to nonintact skin, LET gel is generally preferred over TAC because of its superior safety record and cost-effectiveness. EMLA (eutectic mixture of local anesthetics) is perhaps the most well-known topical anesthetic for use on intact skin. EMLA can be used to anesthetize the skin before intramuscular injections, venipuncture, and simple skin procedures such as curettage or biopsy. To be fully effective, EMLA should be applied at least 90 minutes before the procedure. ELA-Max is a new, rapidly acting topical agent for intact skin that works by way of a liposomal delivery system and is available over the counter. Other delivery vehicles for topical anesthesia currently in development, including iontophoresis and anesthetic patches, may one day give patients and physicians even more flexibility.

PMID: 12126037 [PubMed - indexed for MEDLINE]

Radial artery cannulation: topical amethocaine gel versus lidocaine infiltration.

Br J Anaesth. 2002 Apr;88(4):580-2

Authors: Olday SJ, Walpole R, Wang JY

BACKGROUND: In a prospective randomized study, we compared topical 4% amethocaine gel (Ametop) with 2% lidocaine infiltration for analgesia for radial artery cannulation. A previous study had shown topical analgesia with EMLA cream reduced pain, shortened cannulation time, and improved success rates when compared with lidocaine infiltration. METHODS: One hundred adult patients undergoing elective cardiac surgery were randomized. Cannulation times and success rates were compared between the two groups. The quality of analgesia was assessed using a visual analogue scale (VAS) and four-point verbal pain scoring system. RESULTS: Ninety-nine sets of data were analysed using Mann-Whitney U and chi-squared tests. Mean time to cannulation was 56 s in the amethocaine group (interquartile range (IQR) 41-142) and 59 s in the lidocaine group (IQR 40-105). The median pain score on the VAS was 2 in both groups (IQR 1-3.5 for amethocaine and 0-4 for lidocaine). CONCLUSIONS: There was no significant difference between these two methods of analgesia for any measured variable.

PMID: 12066736 [PubMed - indexed for MEDLINE]

A clinical study to evaluate the efficacy of ELA-Max (4% liposomal lidocaine) as compared with eutectic mixture of local anesthetics cream for pain reduction of venipuncture in children.

Pediatrics. 2002 Jun;109(6):1093-9

Authors: Eichenfield LF, Funk A, Fallon-Friedlander S, Cunningham BB

OBJECTIVE: A double-randomized, blinded crossover trial was performed to assess the efficacy of ELA-Max (4% liposomal lidocaine) as compared with eutectic mixture of local anesthetics (EMLA) for pain relief during pediatric venipuncture procedures. Safety was assessed by evaluation for topical or systemic effects and measurement of serum lidocaine concentrations. METHODS: A total of 120 children who were scheduled for repeat venipuncture for non-study-related reasons at 2 sites participated in the study. Patients were doubly randomized to treatment regimen (study medication application time of either 30 or 60 minutes) and to the order of application of the topical anesthetics for each venipuncture. The primary outcome measures were the child's rating of pain immediately after the venipuncture procedures using a 100-mm visual analog scale (VAS) tool and the parent's and blinded research observer's Observed Behavioral Distress scores. RESULTS: Both ELA-Max and EMLA seemed to alleviate venipuncture pain. There was no clinically or statistically significant difference in the patient VAS scores within the 30-minute or 60-minute treatment groups, and there was no clinical or statistical difference in VAS scores between the 30-minute ELA-Max treatment without occlusion and the 60-minute EMLA treatment with occlusion. There were no clinically or statistically significant differences between treatment with ELA-Max and EMLA in parental or blinded researcher Observed Behavioral Distress scores, the most frequent response at any observation time being "no distress." CONCLUSION: This study demonstrates that a 30-minute application of ELA-Max without occlusion is as safe and as effective for ameliorating pain associated with venipuncture as a 60-minute application of the prescription product EMLA requiring occlusion.

PMID: 12042548 [PubMed - indexed for MEDLINE]

Lidocaine iontophoresis versus eutectic mixture of local anesthetics (EMLA) for IV placement in children.

Anesth Analg. 2002 Jun;94(6):1484-8, table of contents

Authors: Galinkin JL, Rose JB, Harris K, Watcha MF

Pain during venipuncture is a major source of concern to children and their caretakers. Iontophoresis is a novel technique that uses an electrical current to facilitate movement of solute ions (lidocaine) across the stratum corneum barrier to provide dermal analgesia. In this study, we compared dermal analgesia provided by lidocaine iontophoresis and eutectic mixture of local anesthetics (EMLA). After informed consent, 26 children, aged 7-16 yr, who required venous cannulation on multiple occasions, were enrolled in this prospective, randomized, crossover study to receive EMLA and iontophoresis on separate occasions. During a third session, each subject received his or her preferred treatment. Pain during venipuncture was assessed by the subject, parent, observer, and technician performing the procedure, by use of a 100-mm visual analog scale. The observer also used the Children's Hospital of Eastern Ontario Pain Scale to rate the subject's pain. Ratings of subject satisfaction were also assessed. There were no significant differences between the two groups in the subject-rated visual analog scale or the Children's Hospital of Eastern Ontario Pain Scale scores. Eleven (50%; 95% confidence interval [CI], 31%-69%) of the 22 subjects who completed both sessions preferred iontophoresis. Five subjects (23%; 95% CI, 10%-44%), including two who did not tolerate treatment with iontophoresis, preferred EMLA, and six (27%; 95% CI, 13%-48%) had no preference for the intervention to provide dermal analgesia. We conclude that lidocaine iontophoresis provides similar pain relief for insertion of IV catheters as EMLA and is a useful noninvasive alternative to establish dermal analgesia for venous cannulation. IMPLICATIONS: Iontophoresis is a technique that uses an electrical current to facilitate movement of solute ions (lidocaine) across the stratum corneum barrier to provide dermal analgesia. Lidocaine iontophoresis provides similar pain relief for insertion of IV catheters as eutectic mixture of local anesthetics and is a useful noninvasive alternative to establish dermal analgesia for venous cannulation.

PMID: 12032012 [PubMed - indexed for MEDLINE]

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation.

J Appl Physiol. 2002 Feb;92(2):780-8

Authors: Berghoff M, Kathpal M, Kilo S, Hilz MJ, Freeman R

The relative contribution of endothelial vasodilating factors to acetylcholine (ACh)-mediated vasodilation in the forearm cutaneous microcirculation is unclear. The aims of this study were to investigate the contributions of prostanoids and cutaneous C fibers to basal cutaneous blood flow (CuBF) and ACh-mediated vasodilation. ACh was iontophoresed into the forearm, and cutaneous perfusion was measured by laser-Doppler flowmetry. To inhibit the production of prostanoids, four doses of acetylsalicylic acid (ASA; 81, 648, 972, and 1,944 mg) were administered orally. Cutaneous nerve fibers were blocked with topical anesthesia. Cyclooxygenase inhibition did not change basal CuBF or endothelium-mediated vasodilation to ACh. In contrast, ASA (972 and 1,944 mg) significantly reduced the C-fiber-mediated axon reflex in a dose-dependent fashion. Blockade of C-fiber function significantly reduced axon reflex-mediated vasodilation but did not affect basal CuBF or endothelium-dependent vasodilation. The findings suggest that prostanoids do not contribute significantly to basal CuBF or endothelium-dependent vasodilation in the forearm microcirculation. In contrast, prostanoids are mediators of the ACh-provoked axon reflex.

PMID: 11796692 [PubMed - indexed for MEDLINE]

The use of EMLA for an intraoral soft-tissue biopsy in a needle phobic: a case report.

Anesth Prog. 2001;48(1):32-4

Authors: Meechan JG

A case is reported of the removal of a leaf fibroma from the mucosa of the hard palate using EMLA topical anesthesia as the sole means of pain control.

PMID: 11495404 [PubMed - indexed for MEDLINE]

[Percutaneous topical anaesthesia applications in ocular surgery]

Arch Soc Esp Oftalmol. 2001 Jul;76(7):437-40

Authors: Grande Baos C

PURPOSE/METHODS: The results of our experience with EMLA cream used as a topical anaesthetic is analysed in a series of forty patients having bilateral and simultaneous oculoplastic procedures, such as the injection of different substances (botulinum toxin, triamcinolone), the removal of superficial skin lesions, or previous to subcutaneous infiltration of local anaesthetics. Patient's reaction to pain and its degree were assessed by the use of topical placebo on the other than EMLA site and compare both subjective and <<objective>> scales. RESULTS/CONCLUSIONS: Patient's discomfort and pain were found to be milder with a statistically significant difference (p<0.0001) compared to placebo when EMLA cream was previously used over the surgical site. Therefore, in our experience, the use of EMLA cream as percutaneous anaesthetic is effective in diminishing pain associated with minor oculoplastic procedures.

PMID: 11438881 [PubMed - indexed for MEDLINE]

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. EMLA or amethocaine (tetracaine) for topical analgesia in children.

Emerg Med J. 2001 May;18(3):209-10

Authors: Boyd R, Jacobs M

PMID: 11354215 [PubMed - indexed for MEDLINE]

A randomised, double-blind, placebo-controlled, comparative study of topical skin analgesics and the anxiety and discomfort associated with venous cannulation.

Br Dent J. 2001 Apr 28;190(8):444-9

Authors: Speirs AF, Taylor KH, Joanes DN, Girdler NM

OBJECTIVES: To compare the effect of topical skin anaesthetic agents on the discomfort and anxiety associated with venous cannulation. DESIGN: Randomised, double-blind, placebo-controlled, within subject, volunteer trial. METHODS: 20 healthy volunteers underwent venous cannulation on three separate occasions having received topical skin application of either 4% amethocaine gel (Ametop), 5% eutectic mixture of lidocaine and prilocaine (EMLA) or E45 cream (placebo). Visual analogue and verbal rating scales were used to assess pain and anxiety associated with the venous cannulation, and anticipated anxiety for future cannulation, under each drug condition. RESULTS: Subjects were aged 22-53 years (mean 32.8 years). The mean visual analogue scores (VAS) for discomfort were found to be significantly lower (p< 0.001) with Ametop (VAS = 18mm) and EMLA (VAS = 29mm) compared with the control (VAS = 38mm). There was a positive correlation (R2 = 72%, p<0.001) between discomfort and the predicted anxiety if cannulation was to be repeated with the same cream. With the placebo a positive correlation (R2 = 19.8%, p = 0.05) was found between the level of anxiety before cannulation and the level of discomfort recorded. CONCLUSIONS: Ametop and EMLA topical anaesthetic agents produce effective skin analgesia for venous cannulation. The use of topical analgesia can reduce perceived anxiety about future cannulation procedures. This has application in the management of anxious patients undergoing intravenous sedation, suggesting that topical analgesia prior to venous cannulation may significantly aid anxiolysis.

PMID: 11352393 [PubMed - indexed for MEDLINE]

The efficacy and safety of EMLA cream for awake fiberoptic endotracheal intubation.

Anesth Analg. 2000 Oct;91(4):1024-6

Authors: Larijani GE, Cypel D, Gratz I, Mroz L, Mandel R, Afshar M, Goldberg ME

EMLA Cream (EC; Astra, Westborough, MA) has been widely used as a local anesthetic. Limited safety information is available with respect to the application of EC to the oral mucous membranes. The purpose of this pilot study was to evaluate the efficacy and safety of EC when applied to oral mucosa for fiberoptic intubation. Twenty ASA physical status I-IV patients (11 women and 9 men), 28-57 yr old, who were scheduled for awake, fiberoptic, intubation participated in this open-label study. A total of 4 g of EC was used for 5 min until the patient showed no evidence of a gag reflex (this was evaluated clinically by the patient's acceptance of the William's airway and considered the endpoint for assessing adequate topicalization of the oropharynx). The measured peak plasma concentration of lidocaine or prilocaine did not reach toxic levels in any patient. Methemoglobin levels did not exceed normal values (1.5%) in any patient, and there was no relationship between methemoglobin levels and patient weight, amount of EC used, measured peak plasma concentration, or times to measured peak concentrations of prilocaine or lidocaine. We conclude that EC provided satisfactory topical anesthesia allowing for successful oral fiberoptic intubation in all patients and should be considered a safe alternative for anesthetizing the airway of patients requiring awake oral fiberoptic intubation.

PMID: 11004069 [PubMed - indexed for MEDLINE]

Relative efficacy of amethocaine gel and lidocaine-prilocaine cream for Port-a-Cath puncture in children.

Pediatrics. 1999 Sep;104(3):e31

Authors: Bishai R, Taddio A, Bar-Oz B, Freedman MH, Koren G

BACKGROUND: Lidocaine-prilocaine cream (EMLA) is currently standard therapy to alleviate procedural pain in children. One of the disadvantages of lidocaine-prilocaine is the need to wait for 60 minutes for adequate skin anesthesia. Amethocaine gel (Ametop) is a new topical anesthetic that requires a shorter application time for skin anesthesia. OBJECTIVES: To compare the relative efficacy and safety of amethocaine gel and lidocaine-prilocaine cream in children with cancer undergoing Port-a-Cath puncture and to determine which patient factors influence judgments about pain. METHODS: Randomized, blinded, crossover study. Each child received either 1 g of amethocaine gel for 30 minutes, preceded by a placebo gel for 30 minutes, or 1 g of lidocaine-prilocaine cream for 60 minutes. Children rated the pain using the faces scale, for which scores ranged from 0 to 5. Parents and attending nurse operators rated pain on a 10-cm visual analog scale. RESULTS: Thirty-nine children participated. The mean age was 10.2 years (range: 5-16 years), and 69% were male. There were no differences in mean pain assessments between amethocaine and lidocaine-prilocaine as rated by the children (2.0 vs 0.5), parents (2.6 vs 6.4), or nurse operators (2.0 vs 0.9). No serious adverse effects were detected with either preparation. Pain scores assigned by parents and children were not influenced by age, gender, duration of diagnosis, or anesthetic regimen (amethocaine versus lidocaine-prilocaine) in the child. Nurses, however, rated pain higher for younger children, and in males during pretreatment with lidocaine-prilocaine. CONCLUSION: Amethocaine achieves similar anesthesia to lidocaine-prilocaine during Port-a-Cath administration in children, with an application time that is half of lidocaine-prilocaine. Pain assessments were not influenced by age, gender, or duration of diagnosis of the child. Nurses may perceive that pain is greater for younger children and in males. lidocaine-prilocaine, amethocaine, pain, children, Port-a-Cath puncture.

PMID: 10469814 [PubMed - indexed for MEDLINE]

Predicting the need for topical anesthetic in the pediatric emergency department.

Pediatrics. 1999 Aug;104(2):e19

Authors: Fein JA, Callahan JM, Boardman CR, Gorelick MH

OBJECTIVE: To investigate the potential for pediatric emergency department (ED) triage nurses to apply a topical anesthetic (ie, eutectic mixture of local anesthetic) for intravenous catheter (IV) insertion. METHODS: Prospective cross-sectional survey over a 2-month period, with post hoc application of internally developed prediction rules. Eligible patients were children presenting to the ED triage area of an urban children's hospital. RESULTS: A total of 2596 (86.7% of eligible children) had a triage nursing prediction performed. Nurse prediction of IV insertion had a sensitivity of 72% (95% CI: 66,78), a specificity of 90% (88,91), and a positive predictive value (PPV) of 49% (44,54). Objective factors such as high-risk medical history (chronic neurologic, hematologic, cardiac, endocrine, or gastrointestinal illness) and high-risk chief complaint (gastrointestinal illness, skin infection, and previous seizure) were incorporated into a predictive score used to predict IV insertion independently with a sensitivity of 33% (27,39) and a PPV of 43% (44,54). Addition of the objective predictors to nursing prediction increased the sensitivity to 76% (70,81) with a PPV of 43% (38,47). Of the patients, 95% received an IV insertion </=45 minutes after triage, 89% </=60 minutes after triage. Of the IV insertions, 68% were placed in the dorsum of the hand. CONCLUSIONS: The prediction of an experienced triage nurse can identify most patients requiring an IV in a pediatric ED. Incorporation of objective criteria other than nursing prediction into this decision process can decrease the amount of wasted product at the expense of less sensitive identification. The timing of IV insertion in our ED would allow for full medication effect of the currently marketed topical anesthetics in the majority of ED patients. topical anesthetic, intravenous cannulation, children, eutectic mixture of local anesthetic.

PMID: 10429137 [PubMed - indexed for MEDLINE]

Efficacy of parental application of eutectic mixture of local anesthetics for intravenous insertion.

Pediatrics. 1999 Jun;103(6):e79

Authors: Koh JL, Fanurik D, Stoner PD, Schmitz ML, VonLanthen M

OBJECTIVE: To demonstrate that parent application of eutectic mixture of local anesthetics (EMLA) results in equal reduction of the pain of intravenous (IV) placement compared with clinician application of EMLA, and to assess potential difficulties with parental application. STUDY DESIGN: A 2 x 2 randomized block design was used, with 41 children divided into two age groups (5-12 years vs 13-18 years) and randomized to one of two experimental groups (parent-applied EMLA vs clinician-applied EMLA). METHODS: All children were scheduled to have outpatient gastrointestinal endoscopies with IV sedation. EMLA was placed at least 60 minutes before IV insertion either by the parent or a clinician, depending on the experimental group assignment. Outcome measures were child pain ratings and observed behavioral distress ratings. Parents and children were interviewed to determine parent and child anxiety levels in anticipation of the IV insertion, previous needle stick experience, and previous difficulty coping. Feasibility outcomes included technical difficulty with application of EMLA and appearance of the EMLA cream and occlusive covering. RESULTS: Pain ratings and behavioral distress ratings in the low to moderate range for all groups and ws and were consistent w previous empiric reports of EMLA outcome. There were no significant differences in pain or distress ratings for either the age or the experimental groups. Parent ratings of their child's previous difficulty coping was related to the level of behavioral distress exhibited before (r =.50), during (r =.32) and after (r =.44) the IV insertion. In addition, children's anxiety ratings about IV insertion seemed to differ among groups (although not statistically significant for post hoc comparisons), with the most anxiety reported by the younger children when clinicians applied the EMLA and by older children when parents applied the EMLA. CONCLUSION: Parent application of EMLA appears to be as effective as clinician application in reducing children's pain and distress associated with IV insertion. Permitting parents to apply the EMLA at home can allow children who are having procedures on an outpatient basis to benefit from topical anesthesia without having to arrive early to the clinic or hospital. Additionally, application by parents may result in less anticipatory anxiety for younger children.

PMID: 10353976 [PubMed - indexed for MEDLINE]

Dorsal penile nerve block vs topical placebo for circumcision in low-birth-weight neonates.

Arch Pediatr Adolesc Med. 1999 May;153(5):476-80

Authors: Holliday MA, Pinckert TL, Kiernan SC, Kunos I, Angelus P, Keszler M

OBJECTIVE: To investigate the efficacy and safety of dorsal penile nerve block (DPNB) and eutectic mixture of lidocaine (EMLA) for palliation of pain associated with circumcision in low-birth-weight infants. DESIGN: Randomized, blinded, controlled trial. SETTING: Intensive care nursery (step down unit) at Georgetown University Medical Center, Washington, DC. PARTICIPANTS: Fifty neonates with weights of 1600 to 2500 g at the time of circumcision who were discharged from the hospital between May 1994 and June 1995 were randomly assigned to the DPNB, EMLA, or control group. Twenty-five infants who were otherwise eligible were excluded because of parental refusal of consent to participate. INTERVENTIONS: Infants in the DPNB and EMLA groups received anesthesia with subcutaneous injection of 1% lidocaine hydrochloride or topical EMLA, respectively. The control group received sham anesthesia with topical placebo (acid mantle cream). MAIN OUTCOME MEASURES: Changes in physiologic variables (heart rate, blood pressure, oxygen saturation, and respiratory rate) and behavioral score 20 minutes before, during, and 5 and 20 minutes after circumcision between DPNB and control groups. Surgical complications and adverse effects were also monitored. RESULTS: Fifty infants were enrolled in the study: 19 randomized to the DPNB group, 19 to the control group, and 12 to the EMLA group. Enrollment into the EMLA group was suspended early because of redness and blistering of the foreskin in 2 infants, and this entire group was excluded from further analysis. The clinical course was similar in all groups of infants. All circumcisions were performed without complication or technical difficulty. Statistically significant differences were noted in heart rate, respiratory rate, and behavioral score when comparing the DPNB group with controls during and after circumcision. CONCLUSION: Dorsal penile nerve block is safe and effective in controlling pain associated with circumcision in low-birth-weight infants.

PMID: 10323627 [PubMed - indexed for MEDLINE]

Digital image analysis of erythema development after experimental thermal injury to human skin: effect of postburn topical local anesthetics (EMLA).

Anesth Analg. 1999 May;88(5):1131-6

Authors: Mattsson U, Cassuto J, Jontell M, J&#xF6;nsson A, Sinclair R, Tarnow P

Local anesthetics inhibit edema and improve circulation in experimental burns. We evaluated the effect of topical local anesthetics on human skin burns in volunteers using computerized color analysis that allowed repeated noninvasive quantitative measurements. A standardized partial-thickness burn (1 cm2) was induced in one forearm of 10 healthy volunteers and in the opposite forearm a week later. The burned areas were treated with lidocaine/prilocaine cream (EMLA; Astra, Sweden) or a placebo cream for 1 h. The experimental skin area was photographed before and 1, 2, 4, and 12 h postburn. Digitized images were evaluated using normalized red-green-blue and Hue-Saturation-Intensity. Differences in erythema between skin treated with EMLA and placebo were not significant during the first 4 h postburn. However, 12 h postburn, a pronounced decrease in the degree of erythema was observed in EMLA-treated skin compared with placebo-treated skin. We conclude that topical local anesthetics administered for 1 h postburn significantly reduces the duration of erythema after a mild thermal injury, which suggests a potential use in clinical practice in the treatment of minor skin burns. IMPLICATIONS: Burn injury constitutes a serious type of tissue damage that activates inflammatory mechanisms, often causing pain, disfiguration, or malfunction. We treated burns using an anesthetic cream and demonstrated a reduction in burn-induced inflammation by using computer-based color image analysis.

PMID: 10320183 [PubMed - indexed for MEDLINE]

Topical lidocaine-prilocaine cream (EMLA) for thoracostomy tube removal.

Anesth Analg. 1999 May;88(5):1107-8

Authors: Valenzuela RC, Rosen DA

We prospectively studied topical lidocaine-prilocaine cream (EMLA) versus IV morphine in a double-blinded, randomized fashion for pain relief during thoracostomy tube (chest tube; CT) removal. Adult patients who had undergone thoracotomy or median sternotomy were randomized to receive either EMLA cream over CT sites transdermally for 3 h or IV morphine 0.5 h before CT removal. Pain behavior was observed and rated before, during, and after CT removal. Pain behavior increased less in the topical EMLA group (mean +/- SE, 4.4+/-0.39) compared with the IV morphine group (6.0+/-0.38; P < 0.01). No signs of infection were noted at the CT sites 24 or 48 h after CT removal. We conclude that EMLA cream is more effective than IV morphine in preventing the pain associated with CT removal. IMPLICATIONS: Postoperatively applying a topical anesthetic cream onto chest tube sites of chest surgery patients 3 h before chest tube removal is more effective than IV morphine in blunting pain response.

PMID: 10320178 [PubMed - indexed for MEDLINE]

Topical anaesthesia of intact skin: liposome-encapsulated tetracaine vs EMLA.

Br J Anaesth. 1998 Dec;81(6):972-3

Authors: Fisher R, Hung O, Mezei M, Stewart R

In this randomized, double-blind study, we have compared the ability of 5% liposome-encapsulated tetracaine (amethocaine) (LET) vs 5% eutectic mixture of local anaesthetics (EMLA) to produce local anaesthesia of intact skin in 40 healthy volunteers. Volunteers had both preparations applied to their forearms under an occlusive dressing for 1 h. Superficial anaesthesia was measured by a total of nine 1-mm pinpricks on each arm. Deeper anaesthesia was assessed by single insertion of a sterile 22-gauge needle to a depth of 3 mm and pain was reported on a visual analogue scale (VAS). If the volunteer perceived greater than four of the 1-mm pinpricks, the 3-mm insertion was not performed. Results showed that the number of pinpricks perceived was significantly less (P < 0.01) for LET (median 1.0; range 0-9) vs EMLA (1.5; 0-9). In volunteers who had deeper anaesthesia assessed, there was no significant difference (P = 0.065) in VAS scores for LET (mean 1.5 (SD 1.4); n = 34) vs EMLA (2.4 (2.1); n = 28). Overall anaesthetic effect, as ranked by all of the subjects, was significantly better for LET compared with EMLA (P = 0.024). We have demonstrated that when applied in equal volumes, 5% LET produced better superficial local anaesthesia than EMLA.

PMID: 10211031 [PubMed - indexed for MEDLINE]

Randomised double blind trial of EMLA for the control of pain related to cryotherapy in the treatment of genital HPV lesions.

Sex Transm Infect. 1998 Aug;74(4):274-5

Authors: Mansell-Gregory M, Romanowski B

OBJECTIVE: To evaluate the efficacy of EMLA (eutectic mixture of local anaesthetic) for the control of pain related to cryotherapy for the treatment of human papilloma virus (HPV) in the outpatient setting. DESIGN: A randomised, double blind, placebo controlled study. SUBJECTS: 40 patients (20 male and 20 female) with external genital HPV involving an area of no greater than 1 cm2. SETTING: The Capital Health Sexually Transmitted Disease Clinic, Edmonton, Alberta, Canada. RESULTS: Patients in whom EMLA was utilised reported significantly lower scores than those in the control group. Women reported pain scores of 4.7/10 and 0.9/10 in placebo and EMLA groups respectively (p < 0.01). Men reported pain scores of 6.4/10 and 3.1/10 in placebo and EMLA groups respectively (p < 0.01). Men reported significantly higher pain scores than women in the EMLA groups (p < 0.01). There was no significant difference in pain scores between men and women in the placebo groups. CONCLUSION: EMLA can provide efficacious topical anaesthesia before cryotherapy for the treatment of external genital HPV.

PMID: 9924468 [PubMed - indexed for MEDLINE]

Topical lidocaine-prilocaine cream (EMLA) versus local infiltration anesthesia for radial artery cannulation.

Anesth Analg. 1998 Aug;87(2):403-6

Authors: Joly LM, Spaulding C, Monchi M, Ali OS, Weber S, Benhamou D

In a randomized trial, we compared topical anesthesia by a lidocaine-prilocaine cream (EMLA; Laboratorie ASTRA, Manterre, France) with subcutaneous local lidocaine infiltration for radial artery cannulation. Patients included 538 adults scheduled for coronary angiography using a radial approach. EMLA was applied 2 h before radial cannulation, and lidocaine infiltration was performed 5 min before cannulation. The primary end point was pain as assessed by a verbal numerical scale (0 = no pain, 10 = extreme pain). Pain was less severe in the EMLA group than in the lidocaine infiltration group (Score of 2 vs 7; P = 0.0001). Additional lidocaine infiltration was required significantly less frequently in the EMLA group (relative risk 0.19). The failure rate of cannulation was significantly lower in the EMLA group (relative risk 0.38), and insertion time was shorter (4 versus 6 min). We conclude that EMLA, compared with lidocaine infiltration, reduces pain associated with radial artery cannulation and improves the success rate of the procedure. Routine application of EMLA should be performed in awake patients 2 h before radial artery cannulation. Implications: In a randomized trial, we compared topical anesthesia by a lidocaine-prilocaine cream (EMLA) with subcutaneous local lidocaine infiltration for radial artery cannulation in 538 adults patients. EMLA reduced pain associated with radial artery cannulation and improved the success rate of the procedure.

PMID: 9706940 [PubMed - indexed for MEDLINE]

[Allergy skin testing after topical anesthesia]

J Pediatr (Rio J). 1996 Jul-Aug;72(4):215-20

Authors: Ferrari FP, Ros&#xE1;rio Filho NA, Schmidt AV

Immediate skin test reactions are the hallmark of atopic diseases. EMLA (eutectic mixture of local anesthetics) is a local anesthetic that reduces the pain and apprehension for skin testing. We studied EMLA effects on the skin prick test with allergen and histamine. Reactions were evaluated by means of wheal and flare crossed diameters, speed of reaction and local temperature changes. One hour occlusion dressing with EMLA significantly delayed the beginning of reaction with antigen (129%) and histamine (101%). It decreased wheal diameter (33% and 15%) as well as local temperature variation (55% and 80%) respectively with antigen and histamine. Local anesthesia with EMLA probably interferes with histamine action and reduces the immediate skin test reaction. Therefore, it should not be used to reduce the pain of allergy skin testing.

PMID: 14688930 [PubMed]

Analgesic and anti-inflammatory effects of lignocaine-prilocaine (EMLA) cream in human burn injury.

Br J Anaesth. 1996 Jun;76(6):806-10

Authors: Pedersen JL, Callesen T, Møiniche S, Kehlet H

Pain relief may be improved by reducing sensitization of nociceptive pathways caused by tissue injury. Such a reduction depends mainly on inhibition of local inflammatory changes and the relation between duration of nociceptive block and nociceptive input. In this study we examined if prolonged topical treatment with local anaesthetics could reduce late hyperalgesia and local inflammation after burn injury in healthy volunteers. The effects of EMLA treatment for 8 h after burn on hyperalgesia, inflammation and wound healing were compared with the contralateral placebo-treated leg for 48 h after bilateral burn injuries (15 x 25 mm, 49 degrees C for 5 min) in a double-blind, randomized study in 12 healthy volunteers. Wound healing was studied 1 and 2 weeks after injury. Neither mechanical nor thermal primary hyperalgesia were affected significantly by prolonged EMLA treatment. Secondary hyperalgesia and skin erythema were also not changed. Seven of 12 placebo-treated legs developed blisters, in contrast with four of 12 EMLA-treated legs. Wound healing showed no apparent differences. Our data suggest that prolonged, topical treatment with local anaesthetics did not reduce local inflammation and late hyperalgesia.

PMID: 8679354 [PubMed - indexed for MEDLINE]

Effect of topical eutectic mixture of local anesthetics on pain response and analgesic requirement during extracorporeal shock wave lithotripsy.

Anesth Analg. 1995 May;80(5):1059

Authors: Bromage PR

PMID: 7726410 [PubMed - indexed for MEDLINE]