Search

BACKGROUND Wet dressings combined with topical corticosteroids are beneficial for patients with generalized and refractory dermatosis; however, to our knowledge, serum levels after topical corticosteroid absorption during intensive therapy have not been reported previously. AIM To examine serum levels of triamcinolone acetonide (TAC) after topical corticosteroid application during intensive wet-dressing therapy. METHODS We performed a retrospective study of adult patients admitted for inpatient wet-dressing therapy from 7 November 2015 to 24 June 2016. Data were collected on sex, age, body surface area, TAC serum levels, number of wet-dressing changes after 24 and 48 h, and type of wet dressing. RESULTS In total, 29 patients (14 men, 15 women) were assessed. Median [interquartile range (IQR)] age was 57 years (51.5-67.0 years) and involved body surface area was 1.98 m2 (1.88-2.15) m2 . Before the 24-hour blood draw, patients had received 1-3 dressing changes. Median (IQR) TAC level at 24 h was 0.33 µg/dL (0.20-0.58 µg/dL), with no significant difference noted between the number of dressing changes and TAC serum level. At 48 h, results of a serum TAC test were available for 22 patients with 2-6 dressing changes. Mean (IQR) serum level was 0.30 µg/dL (0.30-0.87 µg/dL). For each additional dressing change, there was an estimated 0.21 µg/dL increase in TAC serum level (95% CI 0.11-0.31; P

The high doses of oral tacrolimus (TAC) (1,2) necessary to prevent acute rejection (AR) after vascularized composite allotransplantation (VCA) are associated with systemic adverse effects. The skin is the most antigenic tissue in VCA and the primary target of AR. However, the short-term use of topical TAC (Protopic®), as an off-label adjunct to oral TAC, to treat AR episodes pro re nata (PRN), has yielded inconsistent results. There is lack of data on the pharmacokinetics and tissue distribution of topical TAC in VCA, that hampers our understanding of the reasons for unreliable efficacy. Toward this goal, we evaluated the ability of topical TAC to achieve high local tissue concentrations at the site of application with low systemic concentrations. We assessed the pharmacokinetics and tissue distribution of topical TAC (Protopic®, 0.03%) after single or repeated topical application in comparison to those after systemic delivery in rats. Animals received a single topical application of TAC ointment (Group 1) or an intravenous (IV) injection of TAC (Group 2) at a dose of 0.5 mg/kg. In another experiment, animals received daily topical application of TAC ointment (Group 3), or daily intraperitoneal (IP) injection of TAC (Group 4) at a dose of 0.5 mg/kg for 7 days. TAC concentrations in blood and tissues were analyzed by Liquid Chromatography–Mass Spectrometry (LC/MS-MS). Following single topical administration, TAC was absorbed slowly with a Tmax of 4 h and an absolute bioavailability of 11%. The concentrations of TAC in skin and muscle were several folds higher than whole blood concentrations. Systemic levels remained subtherapeutic (< 3 ng/ml) with repeated once daily applications. Topical application of TAC ointment (Protopic®, 0.03%) at a dose of 0.5 mg/kg/day provided high concentrations in the local tissues with low systemic exposure. Repeated topical administration of TAC is well tolerated with no local or systemic adverse effects. This study confirms the feasibility of topical application of TAC for site specific graft immunosuppression and enables future applications in VCA.

Background The authors present a case demonstrating the success of topical tacrolimus (TAC) therapy with custom trays in the treatment of oral chronic graft-versus-host disease (cGVHD). The 41-year-old male patient initially responded to topical steroid therapy (clobetasol propionate 0.05% ointment) applied both topically and with flexible carrier trays, but later became refractory to this potent topical agent. Topical TAC therapy with flexible carrier trays and systemic prednisone therapy was initiated. Results The patient responded favorably with the change to topical TAC therapy with custom trays (and oral prednisone). His oral cGVHD lesions resolved within a period of 4 weeks. The improvement has remained stable at 14 months of follow-up. Clinical implications This is the first case reported with regard to the successful resolution of steroid recalcitrant cGVHD successfully treated with topical TAC with custom trays.

Objective. To compare the effectiveness of four topical anesthetics that do not contain cocaine with that of topical tetracaine-adrenaline-cocaine (TAC) and lidocaine infiltration during laceration repair in children. Design. This was a randomized, blinded trial. Setting. The study was conducted in the emergency department of a large children's hospital. Participants. Subjects were children 2 years of age or older with a laceration 5 cm or less in length that required suturing. Interventions. Patients were randomly assigned to receive one of four noncocaine-containing topical anesthetics, topical TAC, or lidocaine infiltration anesthesia before laceration repair. Outcome Measures. Outcome measures assessed pain perceptions using a Visual Analogue Scale, Likert scale, and Anesthetic Effectiveness scale. Distress behaviors of patients were measured with the Restrained Infants and Children Distress Rating Scale. Results. Two hundred forty patients were enrolled in the study. Using α = 0.05 and β = 0.2, there was statistical power to detect differences of 0.3 to 1.3 U for the outcome measures used. The bupivacaine-norepinephrine topical solution (Bupivanor) performed better than the other three new topical preparations. It provided effective wound anesthesia during laceration repair, especially for lacerations of the face and scalp, where it was consistently rated as effective as TAC and 1% lidocaine infiltration by all observer groups for all outcome measures. There was a 4% overall wound complication rate, including one wound infection. Conclusion. Bupivanor is an effective alternative to TAC and lidocaine infiltration for local anesthesia during laceration repair, especially on the face and scalp. The effectiveness of Bupivanor on the face is important, because it is here where TAC is most likely inadvertently to come into contact with mucous membranes and result in systemic toxicity. Because pain and distress scores did not take into consideration the pain associated with the initial injection of lidocaine, the findings of this study conservatively estimate Bupivanor's effectiveness compared with lidocaine infiltration.

The study objective was to compare the topical anesthetic LAT (4% lidocaine, 1:2,000 adrenaline, 1% tetracaine) to TAC (0.5% tetracaine, 1:2,000 adrenaline, 11.8% cocaine) for efficacy, adverse effects, and costs. The study design was a randomized, prospective, double blind clinical trial set in an inner-city emergency department with an emergency medicine residency program. Adults with linear lacerations of the face or scalp were eligible for inclusion in the study. Patients had lacerations anesthetized with topical TAC or LAT according to a random numbers table. A total of 95 patients were included in the study with 47 receiving TAC and 48 receiving LAT. Patients stated the number of sutures causing pain and patients and physicians rated the overall pain of suturing using a standard visual analog scale (VAS). The power of the study to determine a ranked sum difference of 15 was 0.8. Visual analog scale results and number and percentage of sutures causing pain were compared using Wilcoxon's Rank Sum Test. According to patients, the percentage of sutures causing pain was significantly fewer for LAT than TAC (P = .036, Interquartile Range 0.13 to 0.0 for LAT, 0.25 to 0 for TAC). Physicians found LAT statistically more effective than TAC (P = .0093, Interquartile Range 1 to 0 for LAT, 2 to 0 for TAC) but patients did not report a difference (P = .266, Interquartile Range 1 to 0 for both LAT and TAC). Our cost per application was $3.00 for LAT compared to $35.00 for TAC. Follow-up was accomplished in 91 of 95 patients (95%) with no reported complications for either medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Study objective. The purpose of the present study is to compare LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) to TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for efficacy, side effects, and costs in children aged 5 to 17 years with facial or scalp lacerations. Design. Randomized, prospective, double-blinded clinical trial. Setting. Inner-city Emergency Department with an Emergency Medicine residency program. Patients or other participants. Children aged 5 to 17 years with linear lacerations of the face or scalp. Intervention. After informed consent was obtained patients had lacerations anesthetized with topical TAC or LAT gel according to a random numbers table. Measurements and main results. A total of 95 patients were included in the statistical analysis with 47 receiving TAC and 48 receiving LAT. Physicians and patients/parents separately rated the overall pain of suturing using a modified multidimensional scale for pain assessment specifically for children. Patients/parents also stated the number of sutures causing pain. The power of the study to determine a ranked sum difference of 15 was 0.8. Multidimensional rating scale results and number and percentage of sutures causing pain were compared using Wilcoxon's rank sum test. According to patients no difference could be detected in percent of sutures causing pain in the LAT versus TAC group (P = .51). Using the multidimensional scale, physicians and patients/parents found LAT statistically the same as TAC in effectiveness (P = .80 for physicians and P = .71 for patients). Cost per application was $3.00 for LAT compared to $35.00 for TAC. Follow-up was accomplished in 85 of 95 participants in the study with no reported complications for either medication. Conclusion. LAT gel worked as well as TAC gel for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children.

We compared the effect of topical 0.5% tetracaine, 1:2,000 epinephrine, and 11.8% cocaine (TAC) with 1% lidocaine infiltration on bacterial proliferation in experimental lacerations. Forty-eight lacerations were made on the backs of Hampshire pigs, inoculated by injection with infectious doses of Staphylococcus aureus and randomly anesthetized with either topical TAC or lidocaine infiltration. Wounds were sutured, and quantitative cultures were obtained by excision after 48 hours. The mean log10 bacteria per gram of tissue for wounds anesthetized with TAC was 6.818 (95% confidence interval [CI], 6.07 to 7.54) compared with 6.820 (95% CI, 5.91 to 7.75) for those treated with lidocaine; this difference was not significant (P less than .05 by paired two-tailed t test). The probability of failing to detect an intergroup difference of 0.5 log10 bacteria per gram was less than .0001. TAC does not increase bacterial proliferation more than lidocaine infiltration in contaminated experimental porcine lacerations.

Lacerations requiring sutures are a common surgical emergency in children. Traditional anesthesia prior to suturing has been intradermal lidocaine. TAC (0.5% tetracaine, 1:2,000 adrenalin, 11.8% cocaine) is a topically applied anesthetic. A randomized, placebo-controlled, double-blind clinical study was conducted to test the hypothesis that topical TAC and intradermal lidocaine are equally efficacious with respect to patient compliance with the suturing process, ie, anesthetic application and placement of sutures, and development of wound complications. Patients less than 18 years old, with lacerations 5 cm or less in length, located in well vascularized, nonmucous membrane areas were included. Patients were entered into the intradermal or topical groups; the intradermal group received lidocaine and the topical group was randomized to receive either TAC or placebo. One hundred fifty-one patients were enrolled in the study. There was no significant difference in the rates of successful initial anesthesia with TAC (89%) and lidocaine (79%). TAC was significantly better (P less than .002) with regard to patient compliance with the suturing process than lidocaine or placebo. Seventeen percent of patients who received placebo had initial anesthesia. These results suggest that TAC, when applied correctly, may be the preferred anesthetic for laceration repair in children.

The local anesthetic activity, toxicity, and irritancy of mepivacaine HCl 1 (1-methyl-2′,6′-pipecoloxylidide hydrochloride) and a solution (solution B) containing 2.0% mepivacaine HCl and 1:20,000 levo-nordefrin (levo-2,4-dihydroxyphenyl-3-hydroxy-2-isopropylamine 2 ) have been studied by various methods. By the intracutaneous wheal test in guinea pigs mepivacaine HCl is 2.5 times more active than procaine HCl. The addition of levo-nordefrin produced a slight increase in the local anesthetic activity of the solution. Solution B was found as active as a solution of 2.0% lidocaine + epinephrine 1:100,000 by the same route of administration ( dilution test ). At the 2.0% concentration level in solutions containing epinephrine 1:100,000 the duration of mepivacaine intradermal anesthesia was approximately 25% longer than that produced by lidocaine. Mepivacaine HCl was found to be as active as cocaine HCl by topical application to the rabbit eye. The topical TAC 5 was 0.18%. At 2, 3, 4, and 8% concentrations, mepivacaine HCl injected intraspinally in rabbits produced anesthesia lasting from 17 to 115 minutes (urethral anesthesia). The degree of intraspinal irritancy appears to be somewhat lower than that of lidocaine. By intravenous injection the following LD 50 values for mepivacaine HCl in mice, rabbits, and guinea pigs were obtained: 32±2, 22±2, and 20±1.4 mg/kg, respectively. Mepivacaine is approximately twice as toxic as procaine HCl and 40% less toxic than lidocaine HCl in mice. The subcutaneous LD 50 values were: 260±22, 110±11, and 94±10 mg/kg for mice, rabbits, and guinea pigs, respectively. Solution B and a 3% solution of mepivacaine HCl without levo-nordefrin (solution A) were well tolerated by monkeys and rats when injected intramuscularly or intravenously in single daily doses eighteen times in 21 days. No significant changes were observed in the body weights, blood counts, urinalyses, or blood pressures of the medicated animals at the end of the medication period. No changes attributable to medication with mepivacaine were observed at the autopsies of the medicated animals. By the trypan blue test the threshold irritant concentration 4 of mepivacaine HCl was 3.3%. That of lidocaine HCl, which was tested in parallel, was 1.9%. Lidocaine HCl is therefore approximately 70% more irritant than mepivacaine HCl. Applied topically on the rabbit eye, mepivacaine HCl and lidocaine HCl were well tolerated in concentrations up to 20%. Solution A and solution B produced a slight, transient inflammatory reaction when injected intramuscularly into rabbits in 1.0-cc doses. No lesions at the injection sites were observed at 7 days after the injection. In summary, mepivacaine HCl, which is 2.5 times more active than procaine HCl is only 25% more irritating and is well tolerated locally as well as systemically on repeated subcutaneous or intramuscular administration.

To evaluate a solution of tetracaine (0.5%), adrenaline 1:2,000, and cocaine (11.8%) as a topical anesthetic in the repair of minor lacerations, a prospective randomized study was performed comparing it with lidocaine infiltration. One hundred fifty-eight patients of a primarily pediatric age group were treated in the emergency department of Madigan Army Medical Center. Anesthetic efficacy was subjectively evaluated. Other variables observed were patient/parent acceptance of the anesthesia, time required for surgical repair, and wound complication rates. No significant difference was found in the anesthetic efficacy of topical TAC and lidocaine infiltration. Time for surgical repair was significantly reduced, and patient acceptance of topical TAC was markedly improved over lidocaine infiltration. Wound complication rates were not significantly different. This form of anesthesia has definite benefits for the emergency physician because it results in a more manageable patient, with subsequent reduction in physician time required to treat minor lacerations in pediatric patients.

The topical anesthetic solution TAC (tetracaine, adrenaline, cocaine) has gained widespread acceptance as the preferred local anesthetic for repairing skin lacerations in children. Despite this popularity, there are no universally accepted guidelines for its application. We report the case of a 6-month-old infant who had respiratory distress and seizures after TAC administration. In addition, we surveyed emergency departments within the state of Virginia regarding their guidelines for TAC application in children. Of the 91 hospitals surveyed, 32 (35%) currently administer TAC, and 14 (44%) of these have no guidelines regarding its use. Among the 20 (63%) with restrictions, there is wide variability in the way it is prescribed. TAC solution is a highly potent anesthetic agent with significant toxicity potential. Research into appropriate dosages, absorption, and actions needs to be undertaken before its widespread acceptance as the drug of choice for providing local anesthesia in children.