Evaluation of a low-dose lidocaine iontophoresis system for topical anesthesia in adults and children: a randomized, controlled trial

BACKGROUND: Commonly used classes of topical anesthetics require 30 to 60 minutes to provide effective anesthesia. A new low-dose lidocaine iontophoresis system (LDLIS) may provide topical anesthesia in 10 minutes at a lower dose than previous systems, thereby limiting adverse events. METHODS: This was a prospective, randomized, multicenter, double-blind, placebo-controlled, clinical trial. Adults and children aged 5 to 17 years (inclusive) received a 10-minute ionntophoretic treatment with either lidocaine or a saline placebo before venipuncture or venous cannulation. Intensity of pain associated with venipuncture or venous cannulation was assessed using either a 10-cm Visual Analog Scale (VAS) for adults and children aged 12 to 17 years or the Facial Affective Scale (FAS) for all children enrolled. RESULTS: Five hundred forty-eight patients (276 adults, 272 children) participated. Mean (SD) VAS pain scores were lower in adults who received iontophoresis with lidocaine rather than with placebo (0.77 [1.49] vs 2.52 [2.30], P < 0.001) and in children aged 12 to 17 years (1.50 [1.87] vs 2.58 [2.26], P = 0.001). FAS pain scores were lower among children who received iontophoresis with lidocaine rather than with placebo (0.36 [0.26] vs 0.51 [0.27], P < 0.001). Similar results were found for children stratified by age group (5-7 years: 0.40 [0.30] vs 0.60 [0.31], P = 0.011; 8-11 years: 0.35 [0.27] vs 0.48 [0.27], P = 0.021; 12-17 years: 0.33 [0.21] vs 0.48 [0.24], P = 0.001). Mean (SD) parental ratings of pain on the FAS for children aged 5 to 11 years were also lower for the lidocaine group (0.45 [0.28] vs 0.55 [0.25], P = 0.018). Adverse events were similar between groups and included skin erythema and edema. One patient in the study experienced a partial-thickness burn. CONCLUSION: In this study of adults and children, the LDLIS provided effective topical anesthesia for venipuncture and venous cannulation within 10 minutes.     

Effect of topical anesthetics on needle insertion pain during botulinum toxin type a injections for limb spasticity

Fung S, Phadke CP, Kam A, Ismail F, Boulias C. Effect of topical anesthetics on needle insertion pain during botulinum toxin type A injections for limb spasticity.ObjectiveTo compare pain perception using 3 anesthetics (eutectic mixture of local anesthetics [EMLA], vapocoolant spray, and ice) compared with a control (no anesthetic) during botulinum toxin type A (BTX-A) injections for lower limb spasticity.DesignA placebo-controlled, single-blinded study where each study patient served as their own control.SettingSpasticity clinic.ParticipantsSubjects (N=30) with ankle spasticity who visited the clinic for BTX-A injections in the gastrocnemius muscle were consecutively sampled.InterventionThe gastrocnemius muscle was divided into 4 quadrants and 1 of the 3 different anesthetic agents was applied to each quadrant with 1 quadrant using no anesthetic, control.Main Outcome MeasuresNumerical Rating Scale (NRS) and the Wong-Baker FACES scale.ResultsPain perception using the NRS and FACES scale was significantly lower using ice and EMLA compared with control and spray conditions (P<.05). Pain perception using EMLA and ice was similar. These results indicate that patients experience minimal to moderate pain during BTX-A injections.ConclusionsPain relief offered by EMLA and ice was comparable, suggesting that ice is a more convenient option because of brief application time (compared with EMLA). Spray may have made the patients more sensitive to pain and alternative approaches for using vapocoolant should be considered.     

小丑照护对患儿焦虑疼痛干预效果的Meta分析

目的 通过Meta分析评价小丑照护缓解患儿焦虑、疼痛程度的影响.方法 计算机检索PubMed、Cochrane Library、EMbase、CINAHL、Web of Science、知网、维普和万方数据库,获取小丑照护对患儿焦虑、疼痛程度效果的随机对照研究和类实验性研究,检索时限为建库至2021年2月.2名研究者依...     

Efficacy of topical anesthetics to reduce pain in premature infants during eye examinations for retinopathy of prematurity

BACKGROUND: Eye examinations for retinopathy of prematurity (ROP) are stressful and probably painful, but many ophthalmologists do not apply topical anesthetics because their efficacy in reducing pain has not been established. OBJECTIVE: To evaluate the potential benefits of topical anesthetic eye drops in reducing pain during neonatal eye examination for ROP. METHODS: Neonates born at < or =30 weeks' gestation and expected to have at least 2 examinations for ROP were included. Patients were randomly assigned to receive either proparacaine HCl ophthalmic solution 0.5% or NaCl 0.9% (saline) eye drops prior to an eye examination. In a subsequent examination, each patient received the alternate treatment. Eye drops were prepared in the pharmacy in identical tuberculin syringes, and physicians, nurses, and pharmacists were blinded to the treatment given. Pain was measured using a scoring system with both physical and physiologic measures of pain (Premature Infant Pain Profile [PIPP], possible range 1-21), which has been validated in preterm infants. PIPP scoring was performed simultaneously by 2 nurses: 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum. The same ophthalmologist performed all examinations. RESULTS: Twenty-two patients were studied, with 11 infants receiving proparacaine and 11 receiving saline as the first treatment. Crossover was performed with a median of 17.5 days between treatments. Patients experienced significantly less pain at speculum insertion with proparacaine than with saline (paired difference -2.5 +/- 3.4; p = 0.001). CONCLUSIONS: Topical anesthetic pretreatment reduces the pain response to eye examination for ROP and should become routine practice. Because this is not effective in all infants, additional measures to reduce pain should be taken.     

Comparison of bacteriostatic normal saline and lidocaine used as intradermal anesthesia for the placement of intravenous lines.

Pain with intravenous (IV) insertion is a common fear for preoperative patients. As perianesthesia nurses, we take the necessary measures to minimize the discomfort and anxiety of our patients. Several research studies have found the use of bacteriostatic normal saline (BNS) to produce a less painful, yet equally effective, safer, and less expensive alternative method for intradermal anesthesia. The purpose of this study was to determine whether a difference existed in pain with intradermal injection and pain with venipuncture when intradermal anesthesia was used. Using an experimental design, 221 participants were randomly assigned by lottery convenience sampling into three groups: lidocaine, BNS, and no local anesthesia. Patients were asked to quantify their pain/discomfort level after the intradermal injection and IV insertion using a modified visual analog scale. Significant findings (P = < .05) indicated that BNS was less painful on injection, and both BNS and lidocaine were effective as local anesthetics for IV insertion. This study helped perianesthesia nurses and patients in determining which method of IV insertion is more effective and reasonably acceptable to ensure patient comfort, satisfaction, and positive outcomes.     

A study comparing chloroprocaine with lidocaine for skin infiltration before intravenous catheter insertion

A prospective, double-blind, mixed, crossover study was conducted to determine the perception of pain associated with intradermal lidocaine and chloroprocaine for insertion of an 18-gauge intravenous catheter. A convenience sample of 64 healthy, adult volunteers was used. Each participant received an intradermal injection of lidocaine or chloroprocaine on the dorsum of one hand followed by insertion of an 18-gauge intravenous catheter. The procedure was repeated on the opposite hand with the other anesthetic. Half of the subjects received lidocaine first, and half received chloroprocaine first. Subjects were asked to rate their pain on a 100-mm visual analogue scale immediately after injection of each local anesthetic and immediately after insertion of the catheter. A repeated analysis of variance was used to determine whether there was significant difference in pain associated with the injections and with the insertion of the catheters. There was no significant difference in the amount of pain associated with the intradermal injections (P = .955) or with insertion of an 18-gauge needle (P = .977). Both local anesthetics were effective in reducing pain from the initial injection of the local anesthetics to the insertion of the 18-gauge needle (P = .000).     

Sex differences in pain perception and anxiety. A psychophysical study with topical capsaicin

Much evidence indicates that women experience painful stimuli as more intense than men do. Nevertheless, some data suggest that sustained low-level pain may be more disturbing to men than to women. The current experiment evaluated the hypothesis that pain is more disturbing for men than for women by comparing across genders sensory and emotional aspects of pain evoked by capsaicin. Ten men and 10 women (aged 20-46 years) received topical capsaicin for 30 min on the face in one session and on the ankle in another. The subjects rated on visual analog scales pain intensity, unpleasantness and anxiety each minute during capsaicin application and for 30 min after its removal. During capsaicin application, females rated both pain intensity (P = 0.04) and unpleasantness (P = 0.05) higher than did males. Further, subjects rated pain intensity and unpleasantness higher on the face than on the ankle, although the physical stimulus was the same. Despite their lower pain ratings, men reported more pain-related anxiety than women (P = 0.02) Moreover, men showed a significant positive correlation between anxiety and pain intensity and unpleasantness, whereas women did not. After removing the capsaicin, there was no overall effect of sex on either intensity (P = 0.18) or unpleasantness (P = 0.37) of the residual sensation. However, men still showed a positive correlation between anxiety and the intensity and unpleasantness of the sensation. Our data confirm with the topical capsaicin model that women rate pain higher than men, but despite their lower pain ratings, males have more anxiety related to pain.     

Reducing venipuncture and intravenous insertion pain with eutectic mixture of local anesthetic: a meta-analysis

BACKGROUND: The eutectic mixture of local anesthetics (EMLA), by producing dermal anesthesia through contact with intact skin, has become a major indication for the reduction of pain experienced during venipuncture (VE) and intravenous (IV) insertion. OBJECTIVES: The purpose of the study was to determine the mean effect sizes and moderators of EMLA cream application in reducing VE and IV insertion pain. METHOD: A meta-analysis of 20 studies was conducted to determine the magnitude of the effect of EMLA cream on VE and IV insertion pain. Effect sizes were calculated three ways: weighted, unweighted, and weighted by quality index score. Potential moderating variables of sample age, premedication, therapist control, insertion site, application duration, research design, pain scale, and funding, were investigated for their influence on EMLA's effect. RESULTS: EMLA cream had a large significant effect on VE pain (d = 1.05) with a 95% confidence interval from.92 to 1.34 and a large significant effect on IV insertion pain (d = 1.04) with a 95% confidence interval from.84 to 1.46. Subject age (child versus adult), type of pain scale, number of therapists, location of insertion site, premedication, funding, or study design did not appear to act as effect modifiers. CONCLUSIONS: EMLA cream can significantly decrease VE and IV insertion pain in 85% of the population.     

The use of a topical refrigerant anesthetic to reduce injection pain in children

Early childhood experiences with painful injections may lead to anxiety and fear. These reactions need not develop if steps are taken to reduce the pain associated with injections. The purpose of this study was to assess the efficacy of a refrigerant topical anesthetic in reducing injection pain in preschool children experiencing routine diphtheria-pertussis-tetanus (DPT) immunizations. This double-blind placebo-controlled study was conducted in community health clinics in conjunction with ongoing immunization programs. Ninety subjects, aged 4–5.5 years, were randomly assigned to one of three groups; (a) refrigerant topical anesthetic; (b) placebo topical spray; and (c) no-spray control. Pain was measured subjectively using a four-point visual analogue scale. Both the refrigerant topical anesthetic spray and the placebo spray significantly reduced injection pain. Age was found to be an important factor influencing pain response in this study. Parental anxiety was not a significant factor influencing pain response. In addition, parents were not good at predicting their child's pain. The results of the study support the use of an intervention, such as refrigerant topical anesthetic, as a practical, simple, and effective treatment strategy for reduction of short-term painful procedures like injections.     

State Versus Trait: Validating State Assessment of Child and Parental Catastrophic Thinking About Children's Acute Pain

Pain catastrophizing has emerged as one of the most robust predictors of child pain outcomes. Although assessments of state (ie, situation-specific) pain catastrophizing in children and parents are often used, their psychometric properties are unknown. This study aimed to assess factor structure, reliability, and predictive validity of state versions of Pain Catastrophizing Scales for children and parents relative to corresponding trait versions for child and parental pain-related outcomes. Data were pooled from 8 experimental pain studies in which child and/or parent state catastrophizing (measured immediately before application of a pain stimulus) and trait catastrophizing were assessed in community-based samples of children aged 8 to 18 years (N = 689) and their parents (N = 888) in Dutch or English. Exploratory factor analyses were conducted to examine the underlying factor structure of the state versions of the Pain Catastrophizing Scale for parents/children, revealing a single factor solution that explained 55.53% of the variance for children and 49.72% for parents. Hierarchical linear regression analyses were used to examine relative influence of state versus trait catastrophizing on child and parent pain-related outcomes. Child and parent state catastrophizing were significantly associated with child pain intensity, child state anxiety and parental distress. State catastrophizing scores showed stronger associations than trait scores for most outcomes.

Parents as distraction coaches during i.v. insertion: a randomized study

This study investigated the effectiveness of a brief Distraction Education intervention for parents prior to their preschool children's medical procedures. Forty-four preschool children with chronic non-life-threatening conditions were having intravenous catheters (IVs) placed for medical tests. Parent-child dyads were randomized into two groups. The experimental group received Distraction Education prior to IV insertion; the control group received standard care. Data were analyzed for two phases of the IV procedure. Phase 1 was the preparation for needle insertion; Phase 2 began with needle insertion. Experimental group parents used significantly more distraction than did control group parents during both phases (P < 0.001). There were no group differences for child behavioral distress or self-report of pain. There was a trend toward a group by phase interaction for behavioral distress (P = 0.07); more experimental group children showed decreased behavioral distress over time (from phase 1 to phase 2) than did control group children (P = 0.02).     

Genetic association study of Endothelin-1 and its receptors EDNRA and EDNRB in migraine with aura

The effect of endothelin-1 and its receptors EDNRA and EDNRB in migraine with aura (MA) susceptibility is not established yet. We studied the association between the MA end-diagnosis and three migraine trait components and 32 single nucleotide polymorphisms (SNPs) capturing the variation of endothelin genes in 850 Finnish migraine patients and 890 non-migrainous individuals. The SNPs showing evidence of association were further studied in 648 German migraine patients and 651 non-migrainous individuals. No significant association was detected. However, the homozygous minor genotype (5% in cases) of the EDNRA SNP rs2048894 showed nominal association with MA both in the Finnish sample ( P  = 0.015) and in the pooled sample [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.12–2.32, P  = 0.010] when adjusted for gender and sample origin. The trait age of onset < 20 years was also associated with rs2048894 (OR 1.69, 95% CI 1.13–2.54, P  = 0.011) in the pooled sample. To confirm this finding studies on even larger samples are required.     

静脉预注去氧肾上腺素联合持续泵注对无痛胃肠镜检查患者血流动力学影响的随机对照研究

目的 探讨无痛胃肠镜检查前预防性静脉注射去氧肾上腺素联合持续泵注对检查过程中患者血流动力学的影响。方法 采用前瞻性随机对照研究方法,选取2019年12月10~31日在首都医科大学附属北京友谊医院接受无痛胃肠镜检查的患者72例,利用SPSS的随机数生成器将患者随机分为去氧肾上腺素组(P组)和对照组(C组),每组各36例。P组患者在麻醉诱导给药后,立即缓慢静脉注射去氧肾上腺素50μg,同时开始静脉持续泵注去氧肾上腺素,起始剂量为30μg/min,检查过程中酌情增减泵注速度,以维持平均动脉压(MAP)波动于基础值20%以内,检查结束时停止泵注;C组患者常规给药。比较两组患者检查前、诱导给药后即刻,检查开始3 min、5 min、10 min、15 min、20 min及检查结束时的血流动力学参数(包括收缩压、舒张压、MAP和心率)、脉搏血氧饱和度、检查时间、苏醒时间、麻醉药物及血管活性药等用量和不良反应。结果 因操作方式改变,P组剔除1例。与C组(n=36)相比,P组(n=35)患者在诱导给药后,低血压的发生率较低(2. 9%vs. 36. 1%),差异具有统计学意义(P <0. 001);P组患者的MAP在诱导给药后即刻[(92±13) mmHg vs.(82±13) mmHg,P=0. 030],检查开始3 min[(87±12) mmHg vs.(77±11) mmHg,P=0. 006]、5 min[(84±11) mm Hg vs.(77±9) mm Hg,P=0. 002]、10 min[(89±8) mm Hg vs.(77±9) mm Hg,P <0. 001]、15 min[(90±9) mm Hg vs.(77±9) mm Hg,P=0. 001]、20 min[(88±8) mm Hg vs.(81±10) mm Hg,P=0. 001]、检查结束[(89±9) mm Hg vs.(84±12) mm Hg,P=0. 001]较高,但P组心动过缓(心率<50次/min)的发生率也较高(14. 3%vs. 0),差异具有统计学意义(P=0. 019);C组患者的麻黄碱用量高于P组[0(0,6) mg vs. 0(0,0) mg],差异具有统计学意义(P=0. 004)。但两组患者的脉搏血氧饱和度、胃肠镜检查时间[(20. 9±5. 8) min vs.(21. 3±6. 1) min,P=0. 752]、苏醒时间[0(0,0) min vs. 0(0,0) min,P=0. 921]、麻醉药及阿托品[0(0,0) mg vs. 0(0,0) mg,P=0. 921]等用药相比,差异无统计学意义(P> 0. 05)。结论 在无痛胃肠镜检查前,预防性静脉注射去氧肾上腺素联合持续泵注,可明显减少检查期间低血压的发生率,维持血流动力学稳定,但需警惕心动过缓的发生,必要时静注阿托品处理。     

Laser-assisted Anesthesia Reduces the Pain of Venous Cannulation in Children and Adults: A Randomized Controlled Trial

Objectives: Application of topical anesthetics before intravenous (IV) cannulation is effective yet limited by delayed transdermal absorption. The authors evaluated a handheld laser device to enhance topical anesthetic absorption by ablating the stratum corneum, the major barrier to drug absorption through the skin. The hypothesis was that laser‐assisted anesthesia would reduce the pain of IV cannulation in emergency department (ED) patients. Methods: This was a blinded, randomized, controlled trial. ED patients aged 1 year and older requiring nonemergent IV cannulation were included. Patients were randomized to pretreatment of the skin with laser or sham laser, and standardized venous cannulation was performed on the dorsum of the patients' hands or antecubital fossa. In the experimental group, the area over the target vein was pretreated with a lightweight, portable Er:YAG unit, with a fluence of 3.5 J/cm², a pulse width of 600 microseconds, and a spot diameter of 6 mm. Lidocaine 4% cream was applied to the area immediately after laser application. Five minutes later, the cream was wiped off and a trained nurse inserted an IV catheter. In the control group, a sham laser and lidocaine were used. Pain of laser application and IV cannulation was recorded on age‐appropriate pain scales; presence of infection or abnormal pigmentation was determined at one week. Pain of cannulation was compared using parametric and nonparametric tests. Results: Sixty‐one patients were randomized to laser (30) and sham (31) pretreatment. Mean (± SD) age was 27 (± 21) years, 49% were female, and one half were children younger than 18 years. The mean pain of IV cannulation was significantly less (mean difference, 28.3 mm; 95% confidence interval = 17.9 to 38.7) in patients pretreated with the laser (10.0 mm; 95% confidence interval = 4.4 to 15.6) than with sham laser (38.3 mm; 95% confidence interval = 29.3 to 42.2). The difference in children was also significant. Application of the laser was painless in most patients. No patient developed infection or abnormal pigmentation. Conclusions: Pretreatment of the skin with a laser device followed by a five‐minute topical lidocaine 4% application reduces the pain of IV cannulation in ED adult and pediatric patients.     

Monitoring nociception during general anesthesia with cardiorespiratory coherence

A novel wavelet transform cardiorespiratory coherence (WTCRC) algorithm has been developed to measure the autonomic state. WTCRC may be used as a nociception index, ranging from 0 (no nociception, strong coherence) to 100 (strong nociception, low coherence). The aim of this study is to estimate the sensitivity of the algorithm to nociception (dental dam insertions) and antinociception (bolus doses of anesthetic drugs). WTCRC’s sensitivity is compared to mean heart rate (HRmean) and mean non-invasive blood pressure (NIBPmean), which are commonly used clinical signs. Data were collected from 48 children receiving general anesthesia during dental surgery. The times of dental dam insertion and anesthetic bolus events were noted in real-time during surgeries. 42 dental dam insertion and 57 anesthetic bolus events were analyzed. The change in average WTCRC, HRmean, and NIBPmean was calculated between a baseline period before each event and a response period after. A Wilcoxon rank-sum test was used to compare changes. Dental dam insertion changed the WTCRC nociception index by an average of 14 (82 %) [95 % CI from 7.4 to 19], HRmean by 7.3 beats/min (8.1 %) [5.6–9.6], and NIBPmean by 8.3 mmHg (12 %) [4.9–13]. A bolus dose of anesthetics changed the WTCRC by ?15 (?50 %) [?21 to ?9.3], HRmean by ?4.8 beats/min (4.6 %) [?6.6 to ?2.9], and NIBPmean by ?2.6 mmHg (3.4 %) [?4.7 to ?0.50]. A nociception index based on cardiorespiratory coherence is more sensitive to nociception and antinociception than are HRmean or NIBPmean. The WTCRC algorithm shows promise for noninvasively monitoring nociception during general anesthesia.     

A psychophysical evaluation of the relationship between trait anxiety, pain perception, and induced state anxiety.

The present study examined the interactive effects of state and trait anxiety on pain threshold and subjective pain intensity. State anxiety was manipulated in 15 low trait anxious (LTA) individuals and 17 high trait anxious (HTA) individuals, who rated their anxiety level and subjective pain intensity in response to noxious electrical experimental pain stimuli. A difference in pain threshold between HTA and LTA participants was not found; however, higher state anxiety led to an increase in reported pain intensity for all participants. Furthermore, HTA individuals reported significantly higher levels of anxiety and pain intensity than LTA individuals across all pain and anxiety conditions. There was no interaction between state and trait anxiety on pain perception and anxiety ratings. These findings show an additive rather than synergistic effect between state-trait anxiety and subjective pain intensity. PERSPECTIVE: Use of anxiety-reducing techniques for individuals experiencing pain might reduce the perceived severity/intensity of pain. Furthermore, individuals with higher trait anxiety (a greater disposition to experience anxiety) might benefit from these techniques because higher trait anxious individuals tend to exacerbate perceived pain stimulations more than lower trait anxious individuals.     

Effects of systemic endothelin A receptor antagonism in various vascular beds in men: in vivo interactions of the major blood pressure-regulating systems and associations with the GNB3 C825T polymorphism

OBJECTIVE: We used the orally available endothelin A (ETA) receptor antagonist darusentan to characterize interactions between the major blood pressure-regulating systems in healthy men. Mediators of the endothelin system, the sympathetic nervous system, and the renin-angiotensin system act via G protein-coupled receptors with a possible involvement of the G-protein beta3 subunit (GNB3) C825T polymorphism. We studied the influence of this polymorphism on the responses to ETA antagonism in the presence of endothelin 1 (ET-1), norepinephrine (NA), and angiotensin II (ANGII). METHODS: Thirty-seven individuals were included in a randomized, double-blind, placebo-controlled, crossover trial with 100 mg darusentan. Systemic hemodynamics and plasma ET-1, NA, and ANGII concentrations were assessed. Local studies were performed in the dorsal hand veins (n=18) and skin microcirculation (n=12), respectively. RESULTS: Darusentan lowered systolic and diastolic blood pressure ( P <.001 versus placebo) without any differences according to genotype (mean maximum Delta systolic blood pressure, -7 +/- 2 mmHg for CT/TT versus -5 +/- 3 mmHg for CC, P=.37; mean maximum Delta diastolic blood pressure, -3 +/- 2 mmHg for CT/TT versus -4 +/- 2 mmHg for CC, P=.96). Venoconstriction to ET-1 and NA was not affected by ET A blockade in either group; however, carriers of the 825T allele demonstrated a markedly enhanced venoconstriction to ET-1 and NA (median effective concentration [ED50] for ET-1 after darusentan [placebo]: 2.5 +/- 0.2 pmol/min for CT/TT [2.7 +/- 0.3 pmol/min], P=.42; 3.9 +/- 0.6 pmol/min for CC [4.6 +/- 0.3 pmol/min], P=.42; P=.046 [P=.0005] for CT/TT versus CC) (ED50 for NA after darusentan [placebo]: 5.2 +/- 1.2 ng/min for CT/TT [7.3 +/- 1.2 ng/min], P=.20; 32.9 +/- 7.1 ng/min for CC [19.7 +/- 5.5 ng/min], P=.75; P=.0008 [P=.026] for CT/TT versus CC). Darusentan dilated veins at baseline in CC homozygous subjects (+0.21 +/- 0.05 mm, P=.004 versus placebo). Systemic ET A antagonism inhibited constriction to ET-1 and also to NA and ANGII in the skin microcirculation without differences according to genotype (ET-1, P=.017 for all individuals versus placebo; NA, P=.0005; and ANGII, P=.002). CONCLUSION: GNB3 C825T allele carrier status did not influence systemic hemodynamic or local vascular responses to ET A blockade with darusentan in young, healthy men. However, it determined venoconstriction to exogenous ET-1 and NA. Darusentan markedly inhibited not only ET-1-induced but also NA-induced and ANGII-induced vasoconstriction in the skin microcirculation. In contrast, it had no effects on either ET-1-mediated or NA-mediated venoconstriction, indicating that, in the presence of high local ET-1 concentrations, constrictive endothelin B receptors may be of greater importance in the venous vasculature than has been recognized so far.     

The use of EMLA cream to decrease venipuncture pain in children

Venipuncture is one of the most painful medical procedures for a child, and it is one of the most frequently performed. This literature synthesis reviews evidence for the use of eutectic mixture of local anesthetics (EMLA) cream to reduce the pain children experience during venipuncture. EMLA cream was compared with placebo, iontophoresis, and amethocaine cream and was found to be an effective local anesthetic for pediatric venipuncture pain during both intravenous cannulation and phlebotomy.     

Ultrasound-enabled topical anesthesia for pain reduction of phlebotomy for whole blood donation

BACKGROUND: Ultrasound-facilitated delivery of topical anesthetics has been used to achieve effective anesthesia within 5 minutes for venipuncture and the insertion of intravenous access devices, but has never been studied for blood donation.
STUDY DESIGN AND METHODS: This study was a single-center, prospective, randomized, sham treatment–controlled, single-blinded clinical evaluation. Repeat donors were randomly assigned to undergo treatment with ultrasound and topical anesthetic or sham ultrasound and placebo anesthetic before phlebotomy for whole blood donation. The primary outcome measures were pain assessments using the Verbal Categorical Scale (VCS) and the Visual Analogue Scale and the assessment of skin irritation at the target site.
RESULTS: One-hundred subjects were enrolled and all completed the study. Compared to the sham/placebo control group, donors receiving ultrasound/anesthetic had lower pain scores on the VCS (1.81 ± 0.67 vs. 2.17 ± 0.68; p = 0.01) and Visual Analog Scale (17.2 ± 15.5 vs. 27.6 ± 19.5; p = 0.006). The proportion of subjects in the treatment group who experienced skin irritation (8%) was similar to that in the control group (2%; p = 0.20).
CONCLUSION: Ultrasound-enhanced delivery of topical anesthetic was demonstrated to be a safe means of quickly achieving clinically meaningful reduction in the pain of phlebotomy for whole blood donation compared to sham/placebo treatment.     

Endothelin receptor A -231 G>A polymorphism: no linkage to primary pediatric headache

OBJECTIVE: To assess whether the biallelic -231 G>A polymorphism of the endothelin type A receptor (EDNRA) gene, previously shown to be a marker of increased risk for developing migraine, has a role in the susceptibility to primary pediatric headache. BACKGROUND: Several studies suggest that endothelin has a role in migraine. A recent association study has shown that the biallelic -231 G>A polymorphism of the EDNRA gene is associated to migraine in an elderly population. METHODS: A total of 126 consecutive unrelated pediatric patients affected by primary headache, classified according to the International Headache Society criteria in migraine (migraine with aura, n = 3; migraine without aura, n = 80), and tension-type headache (episodic tension-type headache, n = 36; chronic tension-type headache, n = 7) patients, were recruited to the study. Sixty-seven healthy blood donors were used as a control group. Genomic DNA was extracted from buccal swabs or blood samples and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the above-mentioned polymorphism. Allele and genotype frequencies for primary headache patients were analyzed in comparison with the control group. RESULTS: No significant differences were found in the distribution of the EDNRA -231 G>A polymorphic variant when considering both genotype (migraine chi2 = 2.78, P = .25; tension-type headache chi2 = 3.58, P = .17) and allelic frequencies (migraine chi2 = 1.48, P = .22; tension-type headache chi2 = 0.39, P = .56). Furthermore, no significant genotype-related difference was found in relation to clinical features, such as age at onset, frequency, and length of the attacks. CONCLUSIONS: Our study shows that the -231 G>A polymorphism in the EDNRA gene is neither associated with primary juvenile headache nor significantly correlated with main clinical features characteristic of the headache pathology in pediatric settings.