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Determinants of infant pain responses are important when assessing the efficacy of analgesics. In a randomized controlled trial, 106 infants aged 2 to 6 months were positioned either supine (SUP) on the examination table or held (HLD) by a parent during routine immunization in a community pediatric office. There was no difference between the SUP and HLD infants in duration of crying, facial grimacing or visual analogue scale (VAS) pain scores. Similarly gender did not affect pain response. In contrast, 2-month-old infants displayed more pain during immunization than did 4 or 6-month-old infants.

Study Objectives. To describe the pharmacokinetic disposition of tobramycin in children undergoing stem cell transplantation (SCT) after intravenous administration either every 24 hours or every 8 hours, and to use this information to create initial dosing guidelines for administration every 24 hours in this patient population. Design. Pharmacokinetic analysis of a randomized controlled trial. Setting. The Hospital for Sick Children, Toronto, Ontario, Canada. Patients. Sixty children (< 18 yrs) with febrile neutropenia undergoing stem cell transplantation. Intervention. Patients were randomized to receive intravenous tobramycin either every 24 hours (29 patients) or every 8 hours (31 patients). Initially, they received either 2.5 mg/kg/dose every 8 hours or weight-based doses by age group (< 5 yrs, 9 mg/kg/dose; 5 to < 12 yrs, 8 mg/kg/dose; ≥ 12 yrs, 7 mg/kg/dose) every 24 hours. Measurements and Main Results. Serum tobramycin concentrations were obtained at 2 and 8 hours after the first dose. Initial guidelines for dosing every 24 hours were derived using the parameters from all patients to achieve a maximum serum concentration (Cmax) of 20–22.5 mg/L and a drug-free interval (time during dosing interval when the tobramycin concentration was < 1 mg/L) of at least 4 hours. After the first tobramycin dose, the elimination rate constant (kel) and volume of distribution (Vd) observed in the every-8-hour group (23 patients) were 0.34 ± 0.09 hours−1 and 0.48 ± 0.21 L/kg, respectively. The kel and Vd in the every-24-hour group (22 patients) were 0.43 ± 0.12 hr−1 and 0.43 ± 0.26 L/kg, respectively. Tobramycin Vd varied with age. Initial doses of tobramycin every 24 hours recommended to achieve the target parameters are 10 mg/kg/dose for patients aged 6 months to less than 9 years, 8 mg/kg/dose for those aged 9 to less than 12 years, and 6 mg/kg/dose for those aged 12 years or older. Conclusion. Children undergoing SCT who receive tobramycin every 24 hours should receive an initial dose based on age. Further validation of the proposed dosing guidelines is required.

Background Sucrose is an effective analgesic for procedural pain in preterm infants. It has been hypothesized that its analgesic effects are mediated by the release of endogenous opioid neurotransmitters such as β-endorphin. Objective To determine whether intraoral administration of sucrose was associated with an increase in serum β-endorphin concentrations in preterm infants with a gestation period less than 29 weeks who were not exposed to a painful stimulus. Methods We performed a prospective open-label study in preterm infants admitted to 2 tertiary neonatal intensive care units. Each infant received a single dose of 30% sucrose intraorally during a 1- to 2-minute period. A blood sample was obtained using an indwelling arterial catheter to determine β-endorphin concentration immediately before and 2 to 5 minutes after the commencement of sucrose administration. Results We enrolled 11 preterm infants with a mean ± SD gestational age of 27.2 ± 0.9 weeks and a mean ± SD birth weight of 1018 ± 238 g (1.02 ± 0.24 kg) at a mean ± SD postnatal age of 3.0 ± 2.5 days. The mean ± SD β-endorphin concentration before and after sucrose administration was 60.4 ± 30.5 pg/mL and 57.4 ± 22.4 pg/mL, respectively ( P = .45). No adverse events were observed during the study procedures. Conclusion Intraoral administration of sucrose in preterm infants did not lead to an increase in serum β-endorphin concentrations at a point in time when the analgesic effects of sucrose were presumed to be present.

OBJECTIVE: To determine the relative efficacy of lidocaine—prilocaine and tetracaine for procedural pain in children. METHODS: Systematic review was performed (MEDLINE 1990–June 2001) of all studies comparing the efficacy of these 2 modalities of pain relief in children undergoing painful cutaneous procedures. Search terms included lidocaine, prilocaine, tetracaine, and anesthesia. RESULTS: Eight studies compared lidocaine—prilocaine with tetracaine in children for 4 different procedures: intravenous cannulation, venipuncture, Port-a-Cath puncture, and laser therapy. When used as labeled (60 min for lidocaine—prilocaine, 30 min for tetracaine), the 2 modalities provided similar analgesic efficacy. When both anesthetics were applied for a similar duration of time (40 min, 60 min, 2 h), tetracaine provided superior anesthesia. Tetracaine was commonly associated with erythema, and lidocaine—prilocaine was associated with blanching of the skin. CONCLUSIONS: Lidocaine—prilocaine and tetracaine appear to be comparable for procedural pain relief when used as recommended. Tetracaine is more efficacious than lidocaine—prilocaine when both anesthetics are applied for the same amount of time.

Background: Pain of circumcision is only partially relieved by single modalities, such as penile nerve block, lidocaine-prilocaine cream, and sucrose pacifiers. Objective: To assess the effectiveness of a combination of interventions on the pain response of infants undergoing circumcision. Methods: Cohort study. Group 1 included infants circumcised using the Mogen clamp and combined analgesics (lidocaine dorsal penile nerve block, lidocaineprilocaine, acetaminophen, and sugar-coated gauze dipped in grape juice). Group 2 included infants circumcised using the Gomco clamp and lidocaine-prilocaine. Infants were videotaped during circumcision, and pain was assessed using facial activity scores and percentage of time spent crying. Results: There were 57 infants in group 1 and 29 infants in group 2. Birth characteristics did not differ between groups. Infants in group 1 were older than infants in group 2 (17 days vs 2 days) (P,.001). The mean duration of the procedure was 55 seconds and 577 seconds for infants in group 1 and 2, respectively (P,.001). Facial action scores and percentage of time spent crying were significantly lower during circumcision for infants in group 1 (P,.001). The percentage of time spent crying was 18% and 40% for infants in groups 1 and 2, respectively. No adverse effects were observed in infants in group 1; 1 infant in group 2 had a local skin infection. Conclusions: Infants circumcised with the Mogen clamp and combined analgesia have substantially less pain than those circumcised with the Gomco clamp and lidocaineprilocaine cream. Because of the immense pain during circumcision, combined local anesthesia and analgesia using the Mogen clamp should be considered. Arch Pediatr Adolesc Med. 2000;154:620-623

Background Neonates routinely undergo tissue-damaging interventions as part of medical treatment. The skin is the site of noxious stimulation for many procedures, including circumcision. EMLA (eutectic mixture of local anesthetics) penetrates intact skin and has the potential to reduce pain associated with circumcision. Objectives To determine the effectiveness of EMLA compared to placebo or no treatment as an analgesic for circumcision in male newborns. Search methods The guidelines of the Cochrane Neonatal Review Group were followed. No language restrictions were applied. Three reviewers (AT, KO, AO) agreed through a consensus process on the inclusion of a specific study. Selection criteria Randomized controlled trials assessing the efficacy/effectiveness of EMLA to prevent circumcision associated pain. Behavioral and physiological outcome data were accepted for efficacy/effectiveness. Data collection and analysis Data abstracted from each report included gestational age at birth, timing and dosage regimen of EMLA, control group treatment and outcomes. Abstracted data were verified by the three investigators (AT, KO, AO). Main results During the different stages of the surgical procedure for circumcision, the increase in heart rate was 12 - 27 beats per minute less for the EMLA group compared to placebo. In a single study, neonates treated with EMLA showed a higher oxygen saturation. Although the data from the three studies could not be combined, crying during circumcision was reported as less in the EMLA treated groups. In two studies, facial action was lower in the EMLA treated groups compared to placebo. Authors' conclusions EMLA reduces pain response during circumcision in newborn male infants. Other potentially more effective forms of analgesia for circumcision (such as dorsal penile nerve block, ring block) should be subjected to systematic reviews.

Aim—To evaluate the eVectiveness of paracetamol in decreasing the pain from heel prick. Methods—A prospective randomised double blind placebo controlled trial was conducted of 75 term neonates undergoing heel prick. Sixty to 90 minutes before the procedure neonates received paracetamol orally in a dose of 20 mg/kg (group 1) or an equal volume of placebo (group 2). Heel prick was performed in a standardised manner. Pain assessments were made using per cent facial action (brow bulge, eye squeeze, and nasolabial fold (range 0‐300%) and per cent of time spent crying (range 0‐100%). Results—Thirty eight neonates were enrolled in group 1 and 37 neonates in group 2. There were no significant diVerences in the demographic characteristics between groups. Mean gestational age was 39 (SD 1.4) vs 39.4 (SD 1.2) weeks, p=0.86, mean birthweight 3.45 (SD 0.45) vs 3.44 (SD 0.42) kg; p=0.31 for groups 1 and 2, respectively. Facial action pain scores did not diVer between groups (143.5 (SD 54.2)% vs 131.1 (SD 59.6)%; p=0.38). Cry scores also did not diVer (29.4 (SD 19.9)% vs 26.8 (SD 20.2)%; p=0.60). No adverse eVects were observed. Conclusion—Paracetamol is ineVective for decreasing the pain from heel prick in term neonates. (Arch Dis Child Fetal Neonatal Ed 1998;79:F209‐F211)

Neonatal pain response and adverse effects and maternal anxiety were assessed in 27 infants who were randomly allocated to venepuncture or heel stick. Pain was assessed by nurses using the Neonatal Infant Pain Scale (NIPS) and a three point scale for the mothers. NIPS scores were higher in the heel stick group compared with the venepuncture group. Maternal anxiety was higher before the procedure while perception of an infant's pain was lower in the venepuncture group compared with the heel stick group. Venepuncture is less painful than heel stick in newborn infants undergoing routine blood sampling. Keywords: pain response; heel stick; venepuncture; blood sampling

Preliminary studies suggested that pain experienced by infants in the neonatal period may have long-lasting effects on future infant behaviour. The objectives of this study were to find out whether neonatal circumcision altered pain response at 4-month or 6-month vaccination compared with the response in uncircumcised infants, and whether pretreatment of circumcision pain with lidocaine-prilocaine cream (Emla) affects the subsequent vaccination response.We used a prospective cohort design to study 87 infants. The infants formed three groups--uncircumcised infants, and infants who had been randomly assigned Emla or placebo in a previous clinical trial to assess the efficacy of Emla cream as pretreatment for pain in neonatal circumcision. Infants were videotaped during vaccination done at the primary care physician's clinic. Videotapes were scored without knowledge of circumcision or treatment status by a research assistant who had been trained to measure infant facial action, cry duration, and visual analogue scale pain scores.Birth characteristics and infant characteristics at the time of vaccination, including age and temperament scores, did not differ significantly among groups. Multivariate ANOVA revealed a significant group effect (p0.001) in difference (vaccination minus baseline) values for percentage facial action, percentage cry time, and visual analogue scale pain scores. Univariate ANOVAs were significant for all outcome measures (p0.05): infants circumcised with placebo had higher difference scores than uncircumcised infants for percentage facial action (136.9 vs 77.5%), percentage cry duration (53.8 vs 24.7%), and visual analogue scale pain scores (5.1 vs 3.1 cm). There was a significant linear trend on all outcome measures, showing increasing pain scores from uncircumcised infants, to those circumcised with Emla, to those circumcised with placebo.Circumcised infants showed a stronger pain response to subsequent routine vaccination than uncircumcised infants. Among the circumcised group, preoperative treatment with Emla attenuated the pain response to vaccination. We recommend treatment to prevent neonatal circumcision pain.

In a recent trial, we found that nursing women reported diarrhea in their nursing infants after maternal use of antibiotics. However, because they were told that this could occur during a medication counseling session, the observed effect could have been due to a reporting bias. The objectives of this study were to determine if counseling nursing women about side effects of antibiotic they used could (a) influence the adverse event reporting rate or (b) influence maternal nursing and medication compliance behavior. In a randomized, controlled trial, nursing women calling a teratogen information service for advice about selected antibiotics received one of two possible counseling formats (A and B). Both groups were informed that the antibiotics were safe to use. Mothers in group B were also informed about a theoretical risk of diarrhea in the infant. Mothers later reported clinical events they noted in the infants and judged whether they were due to the antibiotic. Eighty-seven percent ( 54 62 ) of group A subjects compared to 68% ( 52 76 ) of group B subjects reported clinical events in their infants during their antibiotic therapy ( P = 0.017). The incidence of reported diarrhea was 26% in group A compared to 17% in group B ( P = 0.3); 34% of subjects in both groups attributed clinical events to antibiotic therapy ( P = 1.0). Diarrhea was attributed to antibiotic therapy in 13% of group A and 12% of group B subjects ( P = 1.0). No differences were observed between groups in breastfeeding pattern and antibiotic compliance. Breastfeeding women counseled about adverse effects were not more likely to report side effects in their infants or to change nursing behavior and medication compliance.

Using data from one of our randomised trials, we investigated post-hoc whether male neonatal circumcision is associated with a greater pain response to routine vaccination at 4 or 6 months. Pain response during routine vaccination with diphtheria-pertussis-tetanus (DPT) alone or DPT followed by Haemophilus influenzae type b conjugate (HIB) was scored blind. 42 boys received DPT and 18 also received HIB. After DPT, median visual analogue scores by an observer were higher in the circumcised group (40 vs 26 mm, p = 0.03). After HIB, circumcised infants had higher behavioural pain scores (8 vs 6, p = 0.01) and cried longer (53 vs 19 s, p = 0.02). Thus neonatal circumcision may affect pain response several months after the event.

EMLA® (eutectic mixture of lidocaine and prilocaine) cream is currently not recommended for use in infants < 1 month of age because of the potential risk of methemoglobinemia as a result of the o-toluidine metabolite of prilocaine. We studied bioavailability and changes in methemoglobin levels following topical penile exposure to 1 g of EMLA cream for 1 hour in piglets. Lidocaine, prilocaine, and o-toluidine concentrations were measured simultaneously using a high-performance liquid chromatography method. The systemic bioavailability of EMLA was low: 4.0 ± (SD) 4.7% for lidocaine (range 0-13.6; n = 8) and 7.2 ± 5.7% for prilocaine (range 0-14.5; n = 8). The ratio between exposure to o-toluidine with EMLA versus intravenous administration (i.e., AUCemla/AUQv; see text) was also low: 4.2 ± 9.3% (range 0–28.6; n = 9). The mean maximum methemoglobin value after intravenous administration was 1.23 ± 0.64% (range 0.5–3.0; n = 12) and after penile application 0.99 ± 0.36% (range 0.5–2.0; n = 12). The methemoglobin value was elevated significantly above baseline after intravenous administration (p = 0.03), but not after penile application of EMLA. These findings suggest that penile administration of 1 g of EMLA may be safe for neonatal circumcision, but further study is required.

OBJECTIVE: To measure acyclovir concentrations in the breast milk of a lactating woman using the drug for herpes zoster while nursing her 7-month-old infant. METHODS: The maternal dosage of acyclovir was 800 mg five times daily for seven days. Three random breast milk samples collected on the fifth and sixth days of therapy were analyzed for acyclovir concentrations with radioimmunoassay (RIA). RESULTS: Acyclovir concentrations in breast milk ranged from 18.5 μmol (4.16 μg/mL) to 25.8 μmol (5.81 μg/mL). An estimate of the infant's dosage ingested through nursing was 0.73 mg/kg/d, or approximately 1 percent of the maternal dose in milligrams/kilograms/day. The baby was nursed without any signs of adverse effects. CONCLUSIONS: Acyclovir was measured in clinically insignificant concentrations in the milk of a woman receiving large dosages for herpes zoster. Breast feeding continued without adverse effects to the nursing infant.

Study objective Local anesthetics are the main class of analgesics used for pain management during laceration repair and other minor surgeries; however, they are administered by injection, which is painful. Warming local anesthetics has been proposed as a cost-free intervention that reduces injection pain. A systematic review of the effectiveness of this technique has not yet been undertaken. We determine the effectiveness of warming local anesthetics to reduce pain in adults and children undergoing local anesthetic infiltration into intradermal or subcutaneous tissue. Methods We used published articles from MEDLINE (1950 to June 2010), EMBASE (1980 to June 2010), CINAHL (1982 to June 2010), the Cochrane Library (second quarter 2010), International Pharmaceutical Abstracts (1970 to June 2010), and ProQuest Dissertations and Theses database (1938 to June 2010). We included studies with randomized or pseudorandomized designs and healthy subjects or patients receiving subcutaneous or intradermal injection of local anesthetics that were warmed (body temperature) or not (room temperature). Studies of regional anesthesia and intraarticular, spinal, or periorbital administration of local anesthetics were excluded. Data were extracted onto predesigned forms and verified by 2 reviewers. Quality was assessed with the Cochrane risk of bias tool. The primary outcome was self-reported pain as assessed by a visual analog or numeric rating scale. Data were combined with mean differences with 95% confidence intervals (CIs) by using a random-effects model. Results Twenty-nine studies were retrieved for close examination and 19 studies met inclusion criteria. A total of 18 studies with 831 patients could be included in a meta-analysis. Seventeen studies had an unclear risk of bias and 1 had a high risk of bias. A mean difference of −11 mm (95% CI −14 to −7 mm) on a 100-mm scale was found in favor of warming local anesthetics. Subgroup analysis of 8 studies investigating the effect of warming on buffered local anesthetics yielded similar results: −7 mm (95% CI −12 to −3 mm). Conclusion Warming local anesthetics leads to less pain during injection and therefore should be done before administration.

To explore physiological and anxiety responses of caregivers who witness a venipuncture being performed on their child and the effects of caregivers' responses on child pain and distress.Observational study between March 13, 2006, and June 8, 2006.Tertiary-level pediatric emergency department in Toronto, Ontario.Fifty-five caregivers of children aged 1 month to 18 years.Observing a child receive an intravenous cannulation.The caregiver's heart rate, blood pressure, and anxiety (measured using a 10-cm visual analogue scale). Child-caregiver interactions were measured using the Child-Adult Medical Procedure Interaction Scale-Short Form (child age,or = 2 years) or the Measure of Adult and Infant Soothing and Distress (child age,2 years). Child pain was measured using the Faces Pain Scale-Revised.During cannulation, there was a significant increase in a caregiver's heart rate (median maximum difference = 12 beats per minute; P.001) and anxiety (median difference = 2.65 cm; P.001). Mean arterial pressure decreased after cannulation (median difference = 4.4 mm Hg; P = .004). Backward linear regression revealed that 34% of the variability in child cannulation pain was predicted by caregiver anxiety and caregiver distress-promoting behavior; 31% of the variability in a child's distress during cannulation was predicted by caregiver distress-promoting behavior. Caregiver heart rate and anxiety during cannulation and caregiver distress-promoting behavior during recovery accounted for 51% of the variability in the child's distress during recovery.Caregivers witnessing an intravenous cannulation in their child had elevated heart rate, blood pressure, and anxiety. These responses predicted child pain and distress. Future studies should evaluate interventions designed to decrease distress responses in caregivers.

Neonatal circumcision is a painful surgical procedure often performed without analgesia. We assessed the efficacy and safety of 5 percent lidocaine-prilocaine cream (Emla) in neonates undergoing circumcision.We carried out a double-blind, randomized, controlled trial in 68 full-term male neonates: 38 were assigned to receive lidocaine-prilocaine cream, and 30 to receive placebo. One gram of lidocaine-prilocaine or placebo cream was applied to the penis under an occlusive dressing for 60 to 80 minutes before circumcision. Behavioral (facial activity and time spent crying) and physiologic (heart rate and blood pressure) responses were recorded during the procedure. Blood samples were obtained at various times after drug application for measurements of methemoglobin and plasma lidocaine, prilocaine, and o-toluidine (a metabolite of prilocaine).A total of 68 and 59 neonates were included in the safety and efficacy analyses, respectively. Demographic characteristics such as gestational age and birth weight did not differ between the lidocaine-prilocaine and placebo groups. During circumcision, the neonates in the lidocaine-prilocaine group had less facial activity (P= 0.01), spent less time crying (P0.001), and had smaller increases in heart rate (P=0.007) than the neonates in the placebo group. Facial-activity scores were 12 to 49 percent lower during various steps of the procedure in the lidocaine-prilocaine group. As compared with neonates in the placebo group, infants in the lidocaine-prilocaine group cried less than half as much and had heart-rate increases of 10 beats per minute less. Blood methemoglobin concentrations (expressed as a percentage of the hemoglobin concentration) were similar (1.3 percent) in both groups. Lidocaine and prilocaine were detected in plasma in 23 (61 percent) and 21 (55 percent) of the infants treated with lidocaine-prilocaine cream, respectively.Lidocaine-prilocaine cream is efficacious and safe for the prevention of pain from circumcision in neonates.

Objective To evaluate 2 heel lancet devices in terms of pain response and success of the procedure in neonates undergoing the newborn screening test. Design Randomized trial. Setting Tenth level, mother-and-baby unit of a university-affiliated hospital. Patients Eighty term neonates. Interventions Heel lance using either the BD Safety-Flow lancet (SF) or the BD QuikHeel lancet (QH). Main Outcome Measures Facial grimacing score (brow bulge, eye squeezed shut, and nasolabial furrow [range, 0%-100%]), cry duration, duration of the procedure, and number of punctures required to collect the blood. Results Forty neonates were enrolled in each group. There were no differences in the demographic characteristics between groups. During the first skin puncture, the median score (25th-75th percentile) for facial grimacing was 100% (76%-100%) for the SF compared with 73% (42%-100%) for the QH ( P = .02). For cry duration, it was 6 seconds (0-9 seconds) vs 0 seconds (0-6 seconds), respectively ( P = .01). Pain scores during blood collection (ie, squeezing) did not differ between groups ( P = .09). The procedure took less time to perform in the QH group (140 seconds [90-236 seconds]) than in the SF group (215 seconds [137-314 seconds]) ( P = .02). The total crying time was shorter in the QH group (90 seconds [66-196 seconds] vs 148 seconds [92-267 seconds]; P = .03). Thirty-six (90%) of the neonates in the QH group received 1 puncture for blood collection compared with 21 (53%) in the SF group ( P Conclusion The BD QuikHeel lancet is superior to the BD Safety-Flow lancet for blood collection in term neonates undergoing the newborn screening test.

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.

Factors Influencing Childrens, Parents, and Nurses Assessment of Childrens' Pain during Port-A-Cath Puncture

Objective: To evaluate the effectiveness of APAP in decreasing the pain from heel lance. Study Design: A prospective randomized double-blind placebo controlled trial in 75 term neonates undergoing heel lance. 60 to 90 minutes prior to procedure, neonates received APAP orally in a dose of 20mg/kg (Group 1) or equal volume placebo (Group 2). Heel lance was performed in a standardized manner. Pain assessments were made using validated pain scores by a research assistant blinded to the treatment group. Percent facial action [brow bulge, eye squeeze and naso-labial fold, range (0-300%) and percent of time spent crying (range 0-100%)] were scored from videotapes. Results: 38 neonates were enrolled in group 1 and 37 neonates in Group 2. There were no statistically significant differences in the demographic characteristics between groups. Mean gestational age was 39±1.4 vs. 39.4±1.2 weeks, p=0.86; mean birth weight 3.45±0.45 vs. 4.33±0.42kg, p=0.31 for Group 1 and 2 respectively. 10 infants were excluded from the efficacy analysis. In 9, the infants had multiple heel lances (n=5, Group 1; n=4 Group 2) and in one case the video recording was of poor quality (Group 1). Overall, facial action pain scores did not differ between groups (143±54.2% vs. 131.1±59.5%, p=0.38); and cry scores did not differ (29.4±19.8% vs. 26.8±20.2%, p=0.60). Conclusion: APAP is ineffective for decreasing the pain from heel lancing in term neonates. Table

Objective. Neonates routinely undergo painful cutaneous procedures as part of their medical treatment. Lidocaine-prilocaine 5% cream (EMLA) is a topical anesthetic that may be useful for diminishing the pain from these procedures. EMLA is routinely used in children and adults. There is substantial apprehension about its use in neonates because of concerns that it may cause methemoglobinemia. The objective of this review was to determine the efficacy and safety of EMLA as an analgesic for procedural pain treatment in neonates and provide evidence-based recommendations for clinical practice. Methods. Systematic review techniques were used. Studies were identified using manual and computer-aided searches (Medline, EMBASE, Reference Update, personal files, scientific meeting proceedings). Behavioral (eg, facial action, crying) and physiologic (eg, heart rate, oxygen saturation, blood pressure, respiratory rate) outcome data from prospective nonrandomized controlled studies and randomized controlled trials in full-term and preterm neonates were accepted for inclusion to establish efficacy of EMLA. The risk of methemoglobinemia (defined as methemoglobin concentration >5% and requiring medical intervention) was estimated from all prospective studies. Results. Eleven studies of the efficacy of EMLA were included in the analysis. Infant gestational age at the time of delivery ranged from 26 weeks to full-term. Two studies included data from both neonates and older infants. The following procedures were studied: circumcision (n = 3), heel lancing (n = 4), venipuncture (n = 1), venipuncture and arterial puncture (n = 1), lumbar puncture (n = 1), and percutaneous venous catheter placement (n = 1). Nine studies were randomized controlled trials. The total sample size for each study ranged from 13 to 110 neonates. The dose of EMLA used was 0.5 g to 2 g in 9 studies, and was not specified in the others. The duration of application ranged from 10 minutes to 3 hours. The three studies that investigated the efficacy of EMLA for decreasing the pain of circumcision used a randomized controlled trial design. All of them demonstrated significantly reduced crying time during the procedure in the infants in the EMLA group compared with the infants in the control group. Facial grimacing, assessed in two of the studies, was also significantly lower in the EMLA group. Using meta-analytic techniques, the heart rate outcome data for two studies was summarized. Increases in heart rate compared with baseline values were 12 to 27 beats per minute less for the EMLA group than in the placebo group during various stages of the surgical procedure. Three studies that investigated the pain from heel lancing were randomized controlled trials; the other was a nonrandomized controlled study. None demonstrated a significant benefit of EMLA for any of the outcome measures used to assess pain (ie, behavioral pain scores, infant crying, heart rate, blood pressure, respiratory rate, oxygenation parameters). One randomized controlled study of the pain from venipuncture showed that infants treated with EMLA had significantly lower heart rates and cry duration compared with infants treated with a placebo. In one nonrandomized study, a significantly lower behavioral pain score was observed for infants treated with EMLA compared with the control group. Infant heart rate, however, did not differ between the groups. In one randomized controlled study of pain from percutaneous venous catheter placement, EMLA resulted in a significantly lower increase in heart rate and respiratory rate. Behavioral pain scores were significantly lower during arterial puncture in one nonrandomized controlled study. EMLA did not reduce physiologic changes or behavioral pain scores in one randomized controlled trial in infants undergoing lumbar puncture. Meta-analytic techniques revealed that methemoglobin concentrations did not differ between EMLA-treated and placebo-treated infants (weighted mean difference, −0.11%; 95% confidence interval, −0.31% to 0.10%). The incidence of clinically important methemoglobinemia from all prospective studies was 0% (95% confidence interval, 0.0% to 0.2%). There was insufficient data to assess the risk with multiple doses of EMLA. Four studies measured concentrations of lidocaine in the plasma of neonates who had been treated with EMLA. In all cases, concentrations were Conclusions. EMLA diminishes pain during circumcision. It may also diminish the pain from venipuncture, arterial puncture, and percutaneous venous catheter placement; however, efficacy data for these procedures are limited. EMLA does not diminish the pain from heel lancing. Based on available data, EMLA is recommended for the treatment of pain from circumcision but not heel lance. There is insufficient data to recommend its use for other procedures. Single doses do not cause methemoglobinemia. Additional research is recommended in neonates before EMLA is used routinely for procedures other than circumcision and to determine the safety of repeated administration.

Background: The efficacy of sucrose for relieving procedural pain in neonates has been investigated in many studies. To date, no systematic review has been performed. Objectives: To determine (1) the efficacy of sucrose in reducing procedural pain and (2) the most effective dose. Methods: The literature was searched using MEDLINE and EMBASE. Data from all double-blind randomized controlled trials (RCTs) were examined to quantify estimates of efficacy for various sucrose doses and water (placebo). Data were extracted for term and preterm neonates who received heelstick or venipuncture. The primary outcome was the proportion of time crying (mean or median) during the first three minutes after the painful stimulus. Data were combined across studies using a random effects model (Cochrane, 1954), adapted for use with single groups, producing a point estimate and 95% confidence interval (CI) for statistical comparison of results. Results: Thirteen RCTs were identified; eight were rejected as data were inappropriate, not extractable, or the primary outcome was not measured. Five studies provided data on 271 infants. The proportion of time crying and 95% CIs for water and each dose of sucrose were: Table The proportion of time crying did not differ between the 0.18g and water groups(p>0.05). Proportion of time crying for all other sucrose doses was significantly lower than 0.18g and water. Doses of 0.24g or larger did not differ significantly (p>0.05). There were no differences in proportion of time crying between term and preterm neonates. Conclusions: Sucrose reduced the proportion of time crying during painful procedures in neonates. The 0.18g dose of sucrose was ineffective. Doses of 0.24g are as effective as larger doses. There appears to be no addional benefit above 0.5g.

EFFICACY AND SAFETY OF LIDOCAINE-PRILOCAINE CREAM (EMLA) FOR NEONATAL CIRCUMCISION PAIN. † 1071

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

NEONATAL PAIN RESPONSE TO HEEL STICK VS VENEPUNCTURE FOR BLOOD SAMPLING- A RANDOMISED CONTROLLED TRIAL. † 1047

Background: Nifedipine is currently being utilized for the treatment of hypertensive conditions in late pregnancy and in the post-partum period. There are insufficient data, however, on possible adverse effects on the neonate. The objective of this study was to evaluate the safety of neonatal exposure to nifedipine at the time of delivery and in the post-partum period.

Background Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood. A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here. Methods 12 participants 12 to 35 years old were recruited to a prospective open-label pilot trial and treated with 60 mg of standardized G. biloba two times per day for 12 weeks. The criteria for feasibility included successful recruitment, 75% or greater retention, effectiveness and lack of serious adverse reactions. Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Other outcomes included photographs and adverse reactions. Safety was assessed by serum coagulation factors (platelets, PTT, INR) at baseline and week 12. Results After 2 months of recruitment, the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size. Eleven participants completed the trial with 85% or greater adherence to the protocol. The total VASI score improved by 0.5 (P = 0.021) from 5.0 to 4.5, range of scale 0 (no depigmentation) to 100 (completely depigmented). The progression of vitiligo stopped in all participants; the total VASI indicated an average repigmentation of vitiligo lesions of 15%. VETF total vitiligo lesion area decreased 0.4% (P = 0.102) from 5.9 to 5.6 from baseline to week 12. VETF staging score improved by 0.7 (P = 0.101) from 6.6 to 5.8, and the VETF spreading score improved by 3.9 (P < 0.001)) from 2.7 to -1.2. There were no statistically significant changes in platelet count, PTT, or INR. Conclusions The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion; participant retention, safety and effectiveness criteria were also met. Ingestion of 60 mg of Ginkgo biloba BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. Larger, randomized double-blind clinical studies are warranted and appear feasible. Trial Registration Clinical trials.gov registration number NCT00907062