Neonatal circumcision. Randomized trial of a sucrose pacifier for pain control. Comparison of two doses of breast milk and sucrose during neonatal heel prick. Hindmilk for procedural pain in term neonates. "Sucrose analgesia": absorptive mechanism or taste perception? Reduction of pain response in premature infants using intraoral sucrose. Effect of non-sucrose sweet tasting solution on neonatal heel prick responses. Pain-relieving effect of sucrose in newborns during heel prick. Effect of sucrose on crying in response to heel stab. Lingual sucrose reduces the pain response to nasogastric tube insertion: a randomised clinical trial. Oral sucrose and a pacifier for pain relief during simple procedures in preterm infants: a randomized controlled trial. A comparative study of nonpharmacological methods to reduce pain in neonates. Sucrose reduces pain reaction to heel lancing in preterm infants: a placebo-controlled, randomized and masked study. Efficacy and safety of sucrose for procedural pain relief in preterm and term neonates. Sucrose and non-nutritive sucking for the relief of pain in screening for retinopathy of prematurity: a randomised controlled trial. Sweeten, soother and swaddle for retinopathy of prematurity screening: a randomised placebo controlled trial. An evaluation of the effects of sucrose on neonatal pain with 2 commonly used circumcision methods. The effects of comfort care on the pain response in preterm infants undergoing screening for retinopathy of prematurity. A randomized, controlled trial of sucrose analgesia in infants younger than 90 days of age who require bladder catheterization in the pediatric emergency department. The effects of various interventions to newborns on pain and duration of crying. Effect of liposomal lidocaine and sucrose alone and in combination for venipuncture pain in newborns. Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates. Venepuncture is preferable to heel lance for blood sampling in term neonates. Milk-induced hypoalgesia in human newborns. Suckling- and sucrose-induced analgesia in human newborns. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Is pain relief equally efficacious and free of side effects with repeated doses of oral sucrose in preterm neonates? Food intake and oral sucrose in preterms prior to heel prick. Oral sucrose for procedural pain in sick hospitalized infants: a randomized-controlled trial. The efficacy of developmentally sensitive interventions and sucrose for relieving procedural pain in very low birth weight neonates. [Analgesic effects of Emla cream and saccharose solution for subcutaneous injections in preterm newborns: a prospective study of 265 injections]. Efficacy of sucrose to reduce pain in premature infants during eye examinations for retinopathy of prematurity. Sucrose attenuates a negative electroencephalographic response to an aversive stimulus for newborns. Breastfeeding or oral sucrose solution in term neonates receiving heel lance: a randomized, controlled trial. Analgesic effects of oral sucrose and pacifier during eye examinations for retinopathy of prematurity. Beyond dorsal penile nerve block: a more humane circumcision. Sucrose as an analgesic agent for infants during immunization injections. Oral sucrose analgesia for preterm infant venepuncture. Effect of repeated doses of sucrose during heel stick procedure in preterm neonates. Does sucrose analgesia promote physiologic stability in preterm neonates? Effectiveness of sucrose analgesia in newborns undergoing painful medical procedures. Pain reduction on insertion of a feeding tube in preterm infants: a randomized controlled trial. Oral sweet solution reduces pain-related behaviour in preterm infants. Contact and nutrient caregiving effects on newborn infant pain responses. Effectiveness of oral sucrose and simulated rocking on pain response in preterm neonates. [Analgesia when taking heel-lance blood in the newborn]. The analgesic effect of sucrose in full term infants: a randomised controlled trial. Comparison of sucrose and human milk on pain response in newborns. Comparison of oral glucose and sucrose solutions on pain response in neonates. Routine sucrose analgesia during the first week of life in neonates younger than 31 weeks' postconceptional age. Can oral sucrose reduce the pain and distress associated with screening for retinopathy of prematurity? A sugar-coated pacifier reduces procedural pain in newborns. Consistent management of repeated procedural pain with sucrose in preterm neonates: Is it effective and safe for repeated use over time? Analgesic effects of EMLA cream and oral sucrose during venipuncture in preterm infants.
To assess the effectiveness of oral sucrose via a nipple compared with no treatment and dorsal penile nerve block (DPNB) for alleviating pain in neonatal circumcision.
                Randomized control trial. Data analysis performed by investigators blinded to the 3 treatment groups.
                University teaching hospital, General Care Nursery.
                One hundred nineteen full-term male, normal birth weight neonates, 12 hours old or older.
                No treatment (our standard care), DPNB, or oral sucrose prior to circumcision.
                Differences between groups in heart rate and oxygen saturation changes from baseline during specified intervals of the circumcision procedure. Differences between groups in loss of data due to episodes of excessive motion.
                Sucrose gave significant (P < .001) pain relief compared with the no treatment control throughout most of the circumcision and particularly in the early stages of the procedure. Overall, the average difference in the elevation of heart rates during the circumcision operative procedure among the 3 groups and the 95% confidence intervals (CIs) were as follows: control vs DPNB, 27.1 beats/min (17.6, 36.6) and control vs sucrose, 9.7 beats/min (0.1, 19.3). Furthermore, newborns who received either DPNB or sucrose had less loss of oxygen saturation data due to excessive motion during the procedure than the no-treatment controls. The total percentages of lost data due to excessive motion in the 3 groups were 31% for control, 10% for DPNB, and 8% for sucrose. Relative risk and 95% CIs were: DPNB vs control, 0.32 (0.23, 0.43); sucrose vs control, 0.26 (0.18, 0.36). Differences in oxygen saturation among the 3 groups during the circumcision operative procedure were statistically (P < .001), but perhaps not clinically, significant. However, the analysis did not include missing data due to excessive motion, which occurred predominantly in the no-treatment control group.
                Sucrose on a pacifier is an inexpensive and effective method for pain relief in neonatal circumcision when DPNB is not desirable. The aim of the present study was to test analgesic effects of double- versus single-dose breast milk and compare this effect with efficacy of double- versus single-dose sucrose in a group of healthy term newborns during heel prick blood sampling.
                Healthy newborns (n= 142) were consecutively allocated to one of the six groups: group 1, single-dose breast milk; group 2, single-dose sterile water; group 3, single-dose 12.5% sucrose; group 4, two doses breast milk; group 5, two doses sterile water; and group 6, two doses 12.5% sucrose before the heel prick. The medians for crying time and the pain scores according to the neonatal facial coding system were recorded.
                Crying times were 117 s, 126 s, 82 s, 128 s, 117 s, and 95 s in groups 1-6, respectively (P= 0.053). The mean pain scores were 4.60, 5.82, 3.91, 4.94, 5, and 4.05 in groups 1-6, respectively (P= 0.068). There was a significant difference between the groups for mean pain scores at 1 min and 3 min. There was a significant difference between the single-dose sucrose group and single-dose sterile water group at 1 min (P= 0.002). The babies in the sucrose group were active awake, whereas the ones in the breast milk group were asleep before heel prick.
                Two doses of sucrose solution were not superior to single-dose sucrose. Neither single nor double doses of breast milk were effective in relieving pain in neonates. Two milliliters breast milk does not reduce response to pain during minor painful procedures in term neonates even when two doses have been given. Further studies are needed. The aim of this study was to investigate whether repeated doses of hindmilk were effective for pain relief during routine heel stick in term neonates. Infants enrolled in this double-blind placebo-controlled study were randomly assigned to hindmilk, 12.5% sucrose and distilled water groups. Infants were given 1 ml of the test solution 1 minute prior to, immediately before and 1 minute after the heel stick. Pain responses were assessed by physiologic and behavioral parameters and also according to the Neonatal Facial Coding System (NFCS). There were significant reductions in crying time, duration of the first cry and tachycardia, time needed for return to baseline heart rate, and the average and 1- and 5-minute NFCS scores in the hindmilk group when compared with the distilled water group. When the hindmilk group was compared to the sucrose group, only the NFCS scores at 1 and 2 minutes reached statistical significance in favor of the sucrose group. Repeated dose hindmilk administration is an effective analgesic intervention in term newborns during heel stick. Although the analgesic effect of 12.5% sucrose is slightly superior, hindmilk may be considered as a physiologically suitable alternative to sucrose. It remains unclear whether "sucrose analgesia" is related to a pre- or postabsorptive mechanism. In a double blind cross over study sucrose reduced the pain response of preterm infants exposed to heel prick blood samples only when it was administered into the mouth. It was ineffective when administered intragastrically. The potential of sucrose to reduce the pain response in a group of healthy premature infants was investigated. Fifteen infants of 32-34 weeks postmenstrual age were tested in a blind crossover manner on two separate occasions no more than two days apart. Either 1 ml of 25% sucrose solution or sterile water was syringed into the baby's mouth 2 minutes before routine heel lancing. Response to the painful stimuli was measured by duration of cry and by facial expression (pain score). There was a significant reduction in the duration of first cry, the percentage of time spent crying in the 5 minutes after heel prick, and the pain score in the sucrose treated group. It is concluded that sucrose has analgesic effects in healthy premature infants. A substance commercially described as 'sugar free,' used as a sweetener for paracetamol suspension, was evaluated on measures of neonatal pain. Sixty infants were randomly allocated to receive one of four solutions before heel stab blood sampling: sterile water (placebo); 25 or 50% sucrose (weight/volume); and the commercial sweet-tasting solution. There was a significant reduction in crying time and pain score 3 minutes after the painful stimulus in all groups compared with the controls. It is concluded that this sweet-tasting solution has analgesic effects as potent as those of concentrated sucrose solutions. We assessed the effect of sucrose as a pain reliever in a population of newborns when cuddled and comforted during heel prick for diagnosis of phenylketonuria. In addition, the influences of gender, gestational age, postnatal age, ponderal index and behavioural state of the infant before the heel prick were studied, as judged by the neonatal infant pain scale (NIPS) score, on crying time (CT) and subsequent NIPS score. 100 healthy full-term infants were enrolled in this double-blind, randomized controlled trial. Before the heel prick, the newborns, when cuddled by the parent(s), were either given 2 ml 50% sucrose solution or 2 ml sterile water. The sessions were videotaped and analyzed for determination of CT and NIPS scores. The frequency distribution of CT showed a bimodal pattern in both the sucrose and the placebo groups. Sucrose significantly reduced CT and NIPS scores after the heel prick. No influence of gender, gestational age, postnatal age or ponderal index on CT was found. NIPS scores before the heel prick correlated significantly and positively with CT and subsequent NIPS scores in both the sucrose and the placebo groups. Intra-orally administered sucrose given before heel prick can be recommended as a useful pain reliever. Furthermore, the findings indicate that factors calming the newborn and creating low NIPS scores before the procedure can reduce the pain reaction equivalently and additively to sucrose administration. It has been suggested that sucrose acts as an analgesic in the neonatal period. To evaluate this further, 52 infants received either 2 ml of 7.5% sucrose or 2 ml of sterile water before heel stab blood sampling. The duration of crying in response to sampling did not differ in the two groups but was related to level of arousal at the time of stimulation. To determine whether lingual sucrose modifies the pain response to nasogastric tube insertion in preterm infants.
                Randomised, double-blind, placebo controlled clinical trial.
                Special care baby unit.
                20 stable preterm infants who required nasogastric tube insertion for feeding, randomised on 51 occasions.
                Lingual 24% sucrose or water placebo (0.5-2 ml varying with body weight) administered 2 min before nasogastric tube insertion.
                Heart rate, oxygen saturation (SaO2), Neonatal Facial Coding Score and presence or absence of cry.
                Infants who received sucrose demonstrated a significantly lower Neonatal Facial Coding Score during nasogastric tube passage compared with the placebo group (median 1 (range 0-4) vs 3 (0-4), p = 0.004). There was a trend for sucrose-treated infants to have little change in heart rate during nasogastric tube passage compared with the placebo group (mean (SD) -0.73 (23) vs +11 (17), p = 0.055). Mean SaO2 did not change significantly. Pain response measurements quickly returned to baseline after nasogastric tube insertion. Adverse effects, such as apnoea or oxygen desaturation, were few and occurred equally in each group.
                Nasogastric tube insertion induces a pain response comparable with previously reported responses to heel lance in neonates. Single-dose lingual 24% sucrose is effective in reducing the behavioural and physiological pain response to nasogastric tube insertion in preterm infants and it appears to be safe. Previous randomized trials of the analgesic effects of sucrose, glucose, and a pacifier in term neonates have shown that the pacifier resulted in lower pain scores than glucose or sucrose, but the pacifier with and without sucrose did not differ. The current study was designed to assess the analgesic effect of pharmacologic (sucrose, water) and a non-pharmacologic measures (pacifier) in preterm infants and to find whether there is any synergism between these intervention in relieving pain during painful procedures.
                In this double-blind, randomized, controlled study, 36 preterm infants (mean 31 weeks gestational age, range 27 to 36 weeks) were randomly allocated to six different regimens (0.5 mL sterile water with pacifier, 0.5 mL sterile water without pacifier, 0.5 mL sucrose 24% with pacifier, 0.5 mL sucrose 24% without pacifier, pacifier alone and control group) during a stay in intensive care of up to 15 days. Pain scores were measured with the Premature Infant Pain Profile (PIPP), a validated behavioral acute pain scale.
                Of all the regimens, the lowest pain scores occurred with the use of 24% sucrose solution combined with pacifier. The mean pain score for the combination of sucrose with pacifier was 0.7 as compared to 1.4 for the sterile water with pacifier group (P<.05).
                The synergistic effect of the combination of sucrose and non-nutritive sucking was clinically effective and safe in relieving the pain of simple procedures such as venipuncture or heel stick in preterm and term infants, but further research is needed on these interventions alone and in combination with other behavioral interventions in neonates. A randomized study was done to compare non pharmacological methods to reduce the pain of heel pricks in 104 stable term neonates. Non-nutritive sucking (NNS), rocking, massage, sucrose (20 percent), distilled water (DW) and expressed breast milk (EBM) were used as pain reducing agents. Duration of cry and Douleur Aiguë du Nouveau né (DAN) score were used to assess pain. Physiological parameters were also recorded before and after the stimulus. At 30 seconds after the stimulus, the pain scores were lowest in the sucrose group but this was not sustained at 1, 2 and 4 minutes. At 2 and 4 minutes pain scores were lowest in the NNS and rocking groups as compared to sucrose, distilled water, expressed breast milk and massage. The total duration of crying was also lowest in the NNS and rocking groups. Physiological parameters were comparable in all groups. Babies who were in Prechtl State 1 and 2 (sleeping) at the time of stimulus showed significantly lesser response to pain compared to babies who were awake. This was seen in all the intervention groups. In conclusion, our study suggests that rocking or giving a baby a pacifier are more effective non-pharmacological analgesics than EBM, DW, sucrose or massage for the pain of heel pricks in neonates. A calm or sleeping state before a painful procedure also appears to decrease crying and pain scores. In term infants sucrose given by mouth has been reported to reduce duration of crying after a heel prick. This study was designed primarily to investigate the effect of sucrose administered orally immediately before heel lancing on the nociceptive reaction in preterm infants as assessed by change in heart rate and duration of crying. A secondary objective was to document changes in cerebral blood volume during acute pain. We used a randomized, masked, placebo-controlled, crossover trial in a neonatal intermediate care unit in a level 3 perinatal center. The patients studied were 16 preterm infants; birth weight, 900-1900 g; gestational wk, 27-34; corrected postmenstrual age at time of investigation, 33-36 wk. Each infant was assessed twice receiving 2 mL of sucrose 50% or 2 mL of distilled water in random order immediately before heel lance. Heart rate, thoracic movements, and transcutaneous blood gases were monitored continuously. Crying during the procedure was documented by a video-camera. A change in cerebral blood volume was assessed by near-infrared spectroscopy. We found the heart increased by a mean of 35 beats/min (bpm) after sucrose and 51 bpm after placebo (median difference 16 bpm, interquartile range 1-30 bpm, p = 0.005). Infants cried 67% of time after sucrose and 88% after placebo (median difference 10%, interquartile range 3-33%, p = 0.002). Cerebral blood volume decreased in 5 of 14 infants after sucrose and in 6 of 14 infants after placebo (difference not significant). Preterm and acutely ill term neonates who are hospitalized in a neonatal intensive care unit are subjected to multiple frequent invasive and painful procedures aimed at improving their outcome. Although several trials to determine the efficacy of sucrose for managing procedural pain in preterm and acutely ill term neonates have been developed, these have generally lacked methodological rigor and have not provided clinicians with clear practice guidelines.
                To compare the efficacy and safety of three interventions for relieving procedural pain associated with heel lances in preterm and term neonates, and to explore the influence of contextual factors including sex, severity of illness, and prior painful procedures on pain responses.
                In a randomized controlled trial, 190 neonates were stratified by gestational age and then randomized to receive (a) sucrose and nonnutritive sucking (n = 64), (b) sucrose alone (n = 62), or (c) sterile water and nonnutritive sucking (control) (n = 64) to evaluate the efficacy (pain response as measured using the Premature Infant Pain Profile) (Stevens, Johnson, Petryshen, & Taddio, 1996) and safety (adverse events) following a scheduled heel lance during the first week of life. Stratification was used to control for the effects of age on pain response.
                Significant differences in pain response existed among treatment groups (F = 22.49, p <.001), with the lowest mean Premature Infant Pain Profile scores in the sucrose and nonnutritive sucking group. Efficacy of sucrose following a heel lance was not affected by severity of illness, postnatal age, or number of painful procedures. Intervention group and sex explained 12% of the variance in Premature Infant Pain Profile scores. Few adverse events occurred (n = 6), and none of them required medical or nursing interventions.
                The combination of sucrose and nonnutritive sucking is the most efficacious intervention for single heel lances. Research on the effects of gestational age on the efficacy and safety of repeated doses of sucrose is required. Screening is necessary for infants at risk of retinopathy of prematurity. Despite local anaesthetic drops, infants find eye examinations distressing, displaying behavioural and physiological changes indicating acute pain. Oral sucrose and non-nutritive sucking reduce pain responses associated with invasive procedures.
                To evaluate the use of oral sucrose and/or pacifier for reducing pain responses during eye examinations.
                Forty infants <32 weeks gestation or <1500 g birth weight, in two neonatal units, were randomised to one of four interventions administered two minutes before their first screening examination: 1 ml sterile water as placebo (group 1, n = 10), 1 ml 33% sucrose solution (group 2, n = 10), 1 ml sterile water with pacifier (group 3, n = 9), or 1 ml 33% sucrose solution with pacifier (group 4, n = 11). Examinations were videotaped. Two observers, blind to the intervention, assessed recordings. Pain responses were scored using the premature infant pain profile (PIPP).
                The groups were similar in gestation, birth weight, and age at examination. Mean PIPP scores were 15.3, 14.3, 12.3, and 12.1 for groups 1, 2, 3, and 4 respectively. Analysis of variance showed a significant difference in PIPP score between groups (p = 0.023). Infants randomised to pacifiers scored lower than those without pacifiers (p = 0.003). There was no difference between groups receiving sucrose and those receiving water (p = 0.321).
                Non-nutritive sucking reduced distress responses in infants undergoing screening for retinopathy of prematurity. The difference in response was large enough to be detected by a validated assessment tool. No synergistic effect of sucrose and pacifier was apparent in this group. To assess the efficacy of oral sucrose combined with swaddling and non-nutritive suck (NNS) as a method for reducing pain associated with retinopathy of prematurity (ROP) screening.
                Randomised placebo controlled study.
                Tertiary level neonatal intensive care unit.
                40 infants undergoing primary eye examination for ROP screening.
                The control group were swaddled, and received 0.2 ml of sterile water given by mouth using a syringe and a soother. The intervention group were swaddled, and received 0.2 ml of sucrose 24% given by mouth using a syringe and a soother.
                40 infants were included in the study. There was no difference in mean gestational age at birth, mean birth weight or corrected gestational age at first examination between both groups. The sucrose group had a significantly lower median Neonatal Pain, Agitation and Sedation Scale (N-PASS) score during ROP screening, initially following insertion of the speculum (6.5 vs 5, p=0.02) and subsequently during scleral indentation (9.5 vs 7.5, p=0.03). Fewer infants experienced episodes of desaturations or bradycardia in the intervention group (1 vs 4, p=0.18).
                ROP screening is a necessary but recognised painful procedure. Sucrose combined with NNS and swaddling reduced the behavioural and physiological pain responses. However, pain scores remained consistently high and appropriate pain relief for ROP screening remains a challenge. The purpose of this study was to identify the least painful circumcision method.
                The infants were circumcised with either the Mogen or the Gomco procedure and were given a sweetened pacifier or a pacifier dipped in water. All infants had a eutectic mixture of local anesthetic cream applied before circumcision. The duration of the crying and grimacing were measured.
                The Gomco procedure took 1.9 times longer to complete. Infants who were circumcised with the Mogen procedure cried and grimaced far less than infants who were circumcised with the Gomco procedure (P =.0001). Sucrose on a pacifier was far more analgesic than water on a pacifier for infants in the Gomco group.
                On the basis of these and other findings on pain prevention and amelioration, we recommend that a local anesthetic be administered in advance of circumcision and that the Mogen procedure be used, unless contraindicated. We also recommend that infants be given a sweetened pacifier before, during, and after circumcision if the Gomco method is used. The aim of the study was to determine if pain and distress during the retinopathy of prematurity (ROP) screening examination could be ameliorated by providing comfort care.
                This study was a prospective, randomized, controlled trial of 30 stable preterm infants who underwent initial ROP screening examinations. Fourteen study infants were swaddled, held, and given 24% sucrose solution during the examination. Sixteen controls were examined while lying in their cribs. Vital signs (i.e., pulse rate, respiratory rate, and oxygen saturation), crying time, and time for the vital signs to return to baseline values were recorded at different times during the examination.
                The vital signs did not vary significantly between the two groups. The participants in the control group had a trend of longer crying time, but this trend did not reach a level of statistical significance. In addition, The time required for the vital signs to return to their baseline values did not vary significantly.
                ROP screening is very distressful for preterm infants. The routine use of comfort care to reduce pain during the examination could not be supported by this study. To determine whether an oral sucrose solution improves pain response for infants undergoing bladder catheterization in an emergency department (ED) population.
                A randomized, double-blinded study comparing the analgesic effects of a sucrose solution to placebo for infants < or = 90 days of age and requiring bladder catheterization. Infants with prior bladder catheterization, previous painful procedures that day, or neurological or genital abnormalities were excluded. Infants were assigned baseline pain scores and then given 2 mL of sucrose or water 2 minutes before catheterization. Trained pediatric ED nurses rated the infants for pain, presence of cry, and time to return to baseline.
                Eighty-three patients were enrolled; 40 were randomized to sucrose, and 40, to placebo. Baseline pain scores were similar within each age group. Overall, sucrose did not produce a significant analgesic effect. In subgroup analysis, infants 1-30 days of age receiving sucrose showed a smaller change in pain scores (2.9 vs. 5.3, p = 0.035), were less likely to cry with catheterization (29% vs. 72%, p = 0.008), and returned to baseline more rapidly after catheter removal (10 seconds vs. 37 seconds, p = 0.04) compared with infants who received placebo. Infants older than 30 days of age who received sucrose did not show statistically significant differences in pain scores, crying, or time to return to baseline behavior.
                There was no overall treatment effect when using an oral sucrose solution before bladder catheterization in infants younger than 90 days of age. However, infants younger than or equal to 30 days of age who received sucrose had smaller increases in pain scores, less crying, and returned to baseline more rapidly than infants receiving placebo. Older infants did not show an improved pain response with oral sucrose. This study aimed to compare the effects of mother's milk, sucrose and pacifier use to overcome pain during painful interventions to the newborns on the crying time and pain.
                Various non-pharmacological methods are used to overcome the pain associated with painful interventions with newborns.
                A prospective, randomised, controlled study involved 120 newborns in Turkey.
                The population consisted of healthy newborns hospitalised in the gynaecology clinics of Trabzon Delivery and Children's Diseases hospital between February 2007-January 2008. The newborns who had blood sampling by heel stick were divided into four groups: mother's milk, sucrose, pacifier and control groups with 30 newborns in each. Data collection was performed using an information form on the newborn characteristics, which was developed by the researchers in the light of literature, clinical IR ear thermometer ET1 for temperature measurement, OXIMAX N-65 Pulse oxymeter for oxygen saturation and heart rate and neonatal infant pain scale for the measurement of the behavioural responses of newborns. Results.  No differences were determined between the groups for heart rate and oxygen saturation in the newborns during painful interventions (p > 0·05). Sucrose followed by pacifier was the most effective method of reducing the crying time in the newborns.
                The results indicate that all three practices reduce the behavioural responses to pain at a higher rate than in the control group.
                Health care personnel should perform painful interventions to the newborns while the babies are held by their mothers and during the procedure use of sucrose should be the primary choice.
                © 2010 Blackwell Publishing Ltd. To determine the relative effectiveness of liposomal lidocaine, sucrose, and their combination for reducing pain in term newborns.
                Ours was a double-blind, randomized, controlled, double-dummy trial of 330 healthy term newborns. Before venipuncture for the newborn screening test, neonates received (1) 1 g of liposomal lidocaine cream topically, (2) 2 mL of 24% sucrose solution orally, or (3) sucrose and liposomal lidocaine. The facial grimacing score (0-100) was used to assess pain. Adverse events and lidocaine levels were used to assess safety.
                Infant characteristics did not differ among groups. Facial grimacing scores were lower in the sucrose group compared with those in the liposomal lidocaine group (mean difference: -27 [95% confidence interval (CI): -36 to -19; P < .001) and for the sucrose plus liposomal lidocaine group compared with those in the liposomal lidocaine group (mean difference: -23 [95% CI: -31 to -14]; P < .001). The sucrose and sucrose plus liposomal lidocaine groups did not differ (mean difference: -5 [95% CI: -13 to 4]; P = .3). Local skin reactions were not observed, and the incidence of spitting up did not differ between sucrose-exposed and non-sucrose-exposed infants (1.4% vs 2.7%, respectively; P = .22). The mean (SD) plasma lidocaine level was 44.6 (55.3) ng/mL.
                Sucrose was more effective than liposomal lidocaine for reducing pain during venipuncture in newborns. The addition of liposomal lidocaine to sucrose did not confer any additional benefit to sucrose alone. There was no evidence of harm from liposomal lidocaine or sucrose. To assess and compare the analgesic effects of orally administered glucose and sucrose and pacifiers. To determine the synergistic analgesic effect of sucrose and pacifiers.
                Randomised prospective study with validated behavioural acute pain rating scale.
                Maternity ward.
                150 term newborns undergoing venepuncture randomly assigned to one of six treatment groups: no treatment; placebo (2 ml sterile water); 2 ml 30% glucose; 2 ml 30% sucrose; a pacifier; and 2 ml 30% sucrose followed by a pacifier.
                Median (interquartile) pain scores during venepuncture were 7 (5-10) for no treatment; 7 (6-10) for placebo (sterile water); 5 (3-7) for 30% glucose; 5 (2-8) for 30% sucrose; 2 (1-4) for pacifier; and 1 (1-2) for 30% sucrose plus pacifier. Mann-Whitney U test P values for comparisons of 30% glucose, 30% sucrose, pacifier, and 30% sucrose plus pacifier versus placebo (sterile water) were 0.005, 0.01, <0.0001, and <0.0001, respectively. Differences between group median pain scores for these comparisons were 2 (95% confidence interval 1 to 4), 2 (0 to 4), 5 (4 to 7), and 6 (5 to 8), respectively. P values for comparisons of 30% glucose, 30% sucrose, and 30% sucrose plus pacifier versus pacifier were 0.0001, 0.001, and 0.06, respectively. Differences between group medians for these comparisons were 3 (2 to 5), 3 (1 to 5), and 1 (0 to 2), respectively.
                The analgesic effects of concentrated sucrose and glucose and pacifiers are clinically apparent in newborns, pacifiers being more effective than sweet solutions. The association of sucrose and pacifier showed a trend towards lower scores compared with pacifiers alone. These simple and safe interventions should be widely used for minor procedures in neonates. The analgesic effect of oral sucrose in newborn infants undergoing painful procedures is generally accepted. For blood sampling, some studies have shown that venepuncture (VP) is less painful than heel lance (HL).
                To determine the least painful and most effective method among blood sampling by VP or HL with or without sucrose.
                Randomised, double blind, placebo controlled trial.
                A total of 100 healthy, full term newborn infants being screened for inborn errors of metabolism were randomly allocated to one of four experimental groups (25 infants in each). Intervention and
                Seven specially trained nurses took turns to carry out blood sampling two minutes after administration of oral sucrose or water. Neonatal pain was assessed by the neonatal facial coding system (NFCS), as well as by crying.
                Without sucrose, the NFCS score was higher in the HL group than the VP group during blood sampling (median 58 v 23, p<0.001). Oral sucrose significantly reduced the score of the HL group (58 v 47, p<0.01) and also tended to reduce the score of the VP group (23 v 2, p<0.1). However, the HL with sucrose group still had a higher score than the VP without sucrose group (47 v 23, p<0.01). Crying and the total procedure time showed the same trends as the NFCS score.
                VP is less painful and more effective than HL for blood sampling in newborn infants. Although oral sucrose may have an additive analgesic effect, it is not necessarily required if VP is used for blood sampling. To determine whether milk and its components reduce crying in newborns during and after blood collection for phenylketonuria evaluation.
                Seventy-two normal newborns ingested 2 mL of milk (Similac), Ross Special Formula, fat, protein, lactose, sucrose, or water for the 2 minutes preceding blood collection via heel lance. Crying duration during and for the 3 minutes after the procedure was determined by scorers who were blind to the ingestive substance.
                Sucrose and Similac each reduced crying during the blood collection procedure. Sucrose, fat, protein, and Ross Special Formula were effective during the 3-minute recovery period. Neither water nor lactose were effective during or after blood collection.
                Milk and some of its components are antinociceptive in human newborns. Based on previous studies, reduced crying during and after painful stimulation may be mediated through endogenous opioids. These findings are of potential clinical significance: natural protective mechanisms, normally engaged during suckling, may safely and noninvasively be activated to reduce newborn crying to painful stimulation. This experiment had three goals: 1. To identify the basis of sucking-induced analgesia in healthy, term, newborn humans undergoing the painful, routine, procedure of heel lance and blood collection. 2. To evaluate how taste-induced and sucking-induced analgesias combine to combat pain. 3. To determine whether facial grimacing was an accurate index of diminished pain, or whether it was linked to tissue trauma. We report that: 1. Sucking an unflavored pacifier was analgesic when and only when suck rate exceeded 30 sucks/min. 2. The combination of sucrose and nonnutritive sucking was remarkably analgesic; we saw no behavioral indication in nine of the ten infants that the heel lance had even occurred. 3. Grimacing was reduced to almost naught by procedures that essentially eliminated crying and markedly reduced heart rate during the blood harvesting procedure. Many infants admitted to hospital undergo repeated invasive procedures. Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores. We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants.
                In this double-blind, randomised controlled trial, 59 newborn infants at University College Hospital (London, UK) were randomly assigned to receive 0·5 mL 24% sucrose solution or 0·5 mL sterile water 2 min before undergoing a clinically required heel lance. Randomisation was by a computer-generated randomisation code, and researchers, clinicians, participants, and parents were masked to the identity of the solutions. The primary outcome was pain-specific brain activity evoked by one time-locked heel lance, recorded with electroencephalography and identified by principal component analysis. Secondary measures were baseline behavioural and physiological measures, observational pain scores (PIPP), and spinal nociceptive reflex withdrawal activity. Data were analysed per protocol. This study is registered, number ISRCTN78390996.
                29 infants were assigned to receive sucrose and 30 to sterilised water; 20 and 24 infants, respectively, were included in the analysis of the primary outcome measure. Nociceptive brain activity after the noxious heel lance did not differ significantly between infants who received sucrose and those who received sterile water (sucrose: mean 0·10, 95% CI 0·04-0·16; sterile water: mean 0·08, 0·04-0·12; p=0·46). No significant difference was recorded between the sucrose and sterile water groups in the magnitude or latency of the spinal nociceptive reflex withdrawal recorded from the biceps femoris of the stimulated leg. The PIPP score was significantly lower in infants given sucrose than in those given sterile water (mean 5·8, 95% CI 3·7-7·8 vs 8·5, 7·3-9·8; p=0·02) and significantly more infants had no change in facial expression after sucrose administration (seven of 20 [35%] vs none of 24; p<0·0001).
                Our data suggest that oral sucrose does not significantly affect activity in neonatal brain or spinal cord nociceptive circuits, and therefore might not be an effective analgesic drug. The ability of sucrose to reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief.
                Medical Research Council.
                Copyright © 2010 Elsevier Ltd. All rights reserved. The aim of the present study was to examine the efficacy and potential side effects of repeated doses of oral sucrose for pain relief during procedures in NICU. Thirty-three preterm neonates were randomly allocated in blind fashion into two groups, the sucrose group (SG=17) and the control group (CG=16). The responses of neonates to pain and distress were assessed during blood collection on four consecutive assessment (ass.) days. For the first assessment, the neonates did not receive any solution before the blood collection procedure. During the next three days, the SG received oral sucrose (25%; 0.5 ml/kg) and the CG received sterile water, 2 min before each minor acute painful procedure. The neonates were evaluated during blood collection each morning. The assessment was divided into five phases: Baseline (BL), Antisepsis (A), Puncture (P), Dressing (D), and Recovery (R). The neonates' facial activity (NFCS), behavioral state, and heart rate were evaluated. The data analysis used cut-off scores for painful and distressful responses. No side effects of using sucrose were detected. There were significantly fewer SG neonates with facial actions signaling pain than CG neonates in P (ass.2) and in A (ass.3). We found significantly fewer SG neonates in the awake state than CG neonates in P (ass.2 and ass.4). There were significantly fewer SG neonates crying during A (ass.2), P (ass.2 and ass.4), and D (ass.3). There was no statistical difference between-groups for physiological response. The efficacy of sucrose was maintained for pain relief in preterm neonates with no side effects. To investigate the soothing effect of feeding on infants in distress, the effects of 2 mL 15% and 1 mL 25% sucrose given orally 2 min before heel prick in fasting preterms to reduce the pain response were assessed. The effects of milk intake by nasogastric tube were also assessed once during the last hour before heel prick, and the effects of milk intake by nasogastric tube once during the last hour before heel prick together with 1 mL 25% sucrose given orally 2 min before heel prick. The pain response was measured as changes in crying time, behavioural state, skin conductance and heart rate. Each group included 12 healthy preterm infants with a median gestational age of 32 wk and a median postnatal age of 14 d. These infants were randomly studied twice; one in connection with the intervention and once after being given sterilized water. Differences in the measured variables before and during heel prick showed that only the crying time was reduced when the infants received milk or 25% sucrose prior to heel prick (p < 0.05). If the infants received milk and 25% sucrose before heel prick, the crying time and the level of behavioural state were reduced (p < 0.05). The increase from before to during heel prick in skin conductance (number and amplitude of the waves) and heart rate correlated with the crying time (p < 0.01). To determine the efficacy of 25% oral sucrose in the reduction of pain during a heel lance procedure in sick hospitalized infants.
                In a blinded randomized- controlled trial, hospitalized infants were given either 1 mL 25% sucrose or 1 mL water 2 min prior to a heel lance procedure. Pain assessment comprised a four-point facial expression score, incidence and duration of crying, heart rate and oxygen saturation changes.
                A total of 128 infants were included. Facial scores immediately upon heel lance, and at 1 and 2 min in the recovery period were reduced in the treatment (sucrose) group compared to the placebo (water) group (P < 0.05). At other observation points, the differences in facial scores between the two groups of infants did not reach statistical significance. Neither incidence nor duration of crying whilst the blood collection was in progress was significantly reduced by sucrose. In the 3-min recovery period following completion of the blood collection, incidence and duration of crying were significantly less in the treatment group of infants (P < 0.05). Physiological responses of heart rate and oxygen saturation were not attenuated by sucrose at any time point during or following the blood collection.
                Oral sucrose was effective in reducing behavioural responses to pain upon heel lance and in the period following completion of a heel lance procedure in this group of sick hospitalized infants. This simple strategy can be promoted in institutions caring for sick babies, as a method of reducing behavioural responses to procedural pain. Procedural pain management for very low birth weight (VLBW) neonates has been minimal or nonexistent in most neonatal intensive care units (NICUs).
                To compare the efficacy of developmentally sensitive behavioral interventions (nonnutritive sucking via a pacifier, positioning) and sucrose for relieving procedural pain in VLBW infants and to determine the influence of contextual factors (gestational age, postnatal age, birth weight, severity of illness, frequency of painful procedures) on pain response.
                In a prospective randomized crossover trial, pain was assessed in 122 VLBW neonates using the Premature Infant Pain Profile following four randomly ordered interventions during consecutive routine heel lance procedures.
                Significant differences in pain existed among treatment interventions (F = 16.20, p < .0001). The pacifier with sucrose (F = 24.09, p < .0001) and pacifier with sterile water (F = 9.00, p = .003) significantly reduced pain. Prone positioning did not decrease pain (F = 2.24, p = .137). Frequency of painful procedures approached significance in influencing pain response (F = 3.59, p = .01).
                The most efficacious interventions for reducing pain from single painful events were the pacifier with sucrose and the pacifier with sterile water. Research on the efficacy and safety of implementing these interventions, alone and in combination, for repeated painful procedures is needed. In addition, research is needed on the influence of implementing these interventions on pain response and clinical outcomes (e.g., health status and neurodevelopmental status) in VLBW neonates in the NICU. To compare the analgesic effects of non nutritive pacifier sucking, oral administration of a 30% saccharose solution, local application of Emla and their association for subcutaneous injection of erythropoietin (EPO) in preterm infants.
                Our study was a randomised, prospective study conducted over 5 months. Neonates with a gestational age below 33 weeks of gestation and older than 8 days of life were included if they were treated with EPO (three subcutaneous injections per week during 6 weeks). For each consecutive EPO injection, patients were randomised between four groups of intervention: non nutritive pacifier sucking (T), oral administration of 0.2-0.5 ml of a 30% saccharose solution with non nutritive pacifier sucking (S), local application of Emla with non nutritive pacifier sucking (E), and oral administration of 0.2-0.5 ml of a 30% saccharose solution with local application of Emla and with non nutritive pacifier sucking (S + E). Each child was its own control. Pain was assessed with the Newborn Acute Pain scale (DAN) and with the Neonatal Facial Coding System (NFCS).
                Thirty-three neonates were included, representing 265 injections. Distribution was: 41 in group T, 71 in group E, 86 in group S and 67 in group E + S. Mean DAN and NFCS scores were statistically different between groups T, E and S. Analgesic effect of saccharose (-1.05) was greater than Emla (-0.56). Used together, effects were adding up without potentialisation.
                This study shows that the association of non nutritive pacifier sucking with oral administration of saccharose and local application of Emla has a better analgesic effect than each of these three interventions alone for subcutaneous injection of EPO. Eye examinations for retinopathy of prematurity (ROP) are painful to the neonate. The use of topical anesthetic for eye examinations to evaluate ROP is routine in our neonatal intensive care unit (NICU), but does not completely suppress painful responses. Sweet solutions have been shown to reduce procedural pain in newborns.
                To examine whether the addition of sucrose 24% to topical anesthetic improves procedural pain control during the ROP eye examination.
                Neonates born at < or = 30 weeks' gestation were included in this placebo-controlled, double-blind, crossover study. Patients were randomly assigned to receive treatment with either proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sucrose 24% or proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sterile water (placebo) prior to an eye examination. In a subsequent eye examination, each patient received the alternate treatment. Oral sucrose and sterile water were prepared in the pharmacy in identical syringes, and physicians, nurses, and pharmacists in the NICU were blinded to the treatment given. Pain was measured using the Premature Infant Pain Profile (PIPP) scoring system, which measures both physical and physiologic measures of pain, and the scores were simultaneously assessed by 2 study nurses. PIPP scores were recorded 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum. The same ophthalmologist performed all eye examinations. Several different definitions of a pain response were investigated.
                Twenty-three infants were studied, with 12 receiving sucrose and 11 receiving placebo as the first treatment. For 3 of the 5 definitions of pain response, patients experienced significantly less pain at speculum insertion with sucrose than with placebo. After the ROP examination, pain responses were similar with either sucrose or placebo.
                Oral sucrose may reduce the immediate pain response in premature infants undergoing eye examination for ROP. Reports that sweet taste calms crying in newborns and is analgesic against the pain caused by a heel lance served as the basis for this study. Electroencephalographic (EEG) activity, heart rate activity, and infants' facial behaviors were recorded before and after a noninvasive, but noxious, heelstroke (procedure from the Brazelton Neonatal Behavior Assessment Scale). In a randomized and controlled trial, 34 newborns were administered 2 mL of water or sucrose solution before the heelstroke. Frontal EEG asymmetry scores were computed, and power in the 3 to 6 Hz frequency band was analyzed. Infants who received water showed increased relative right frontal EEG activation from baseline to the post-heelstroke phase, a pattern that typifies negative affect. The EEG of infants in the sucrose group did not change. Heart rate increased rapidly in both groups during the heelstroke phase. However, after the heelstroke, the heart rate of infants who received sucrose returned to baseline, whereas the heart rate of infants who tasted water remained elevated. During the heelstroke, the infants in the water group cried and grimaced twice as long as the infants in the sucrose group. These findings add to the growing literature showing that sucrose attenuates newborns' negative response to aversive or noxious stimuli. The purpose of this work was to compare the efficacy of breastfeeding versus orally administered sucrose solution in reducing pain response during blood sampling through heel lance. METHODS; We conducted an open-label, randomized, controlled trial at a neonatal unit of a public hospital in northern Italy on 101 term neonates undergoing heel lance with an automated piercing device for routine neonatal screening for congenital disorders. Newborn infants were randomly assigned to breastfeeding during blood sampling or to the oral administration of 1 mL of 25% sucrose solution. We validated the multidimensional acute pain rating scale of the Premature Infant Pain Profile, heart rate increase, oxygen saturation decrease, crying behavior (duration of first cry, cry percentage in 2 minutes, and during blood sampling), duration of sampling, and the number of performed heel lances.
                Median Premature Infant Pain Profile scores were lower in the breastfeeding group (3.0) than in the sucrose-solution group (8.5), and the median group difference was -5.0. The median heart rate increase, oxygen saturation decrease, and duration of first cry for the breastfeeding group were, respectively, 13.0, -1, and 3 and for sucrose group were 22, -3, and 21. Medians were significantly different between the groups. There were no significant differences in the sampling duration and numbers of heel lances.
                This study suggests that breastfeeding provides superior analgesia for heel lance compared with oral sucrose in term neonates. Oral sucrose reduces pain during heel sticks and venipunctures in preterm infants, but no studies have been done to determine the effectiveness of sucrose during eye examinations for retinopathy of prematurity. Therefore, the purpose of this study was to determine the effectiveness of local anesthetic eye drops and a pacifier, plus repeated doses of 24% sucrose, to relieve pain associated with eye examinations for retinopathy of prematurity. In this double-blind randomized controlled trial, 30 preterm infants were randomly assigned to one of two treatments, in which they received either local anesthetic eye drops, a pacifier, plus three doses of sterile water or local anesthetic eye drops, a pacifier, plus three doses of 24% sucrose during the eye examination. Treatment effectiveness was determined using a validated infant pain measure, the Premature Infant Pain Profile (PIPP), which includes measures of facial expressions, heart rate, and oxygen saturation and takes behavioral state and gestational age into consideration. Data were collected before, during, and following an examination of the left eye. Statistically significant differences in mean PIPP scores were found between the sucrose and water groups during the left eye examination. The mean PIPP score was 8.8 for the sucrose group and 11.4 for the water group ( t = 2.87, p = .008 two-tailed). No significant differences were found in PIPP scores immediately following the procedure. Sucrose and a pacifier may be beneficial for minimizing pain during eye examinations in preterm infants and should be considered as a part of evidence-based guidelines for relieving pain during this procedure. To explore techniques that can be utilized in addition to the dorsal penile nerve block (DPNB) to further reduce the neonate's stress and pain from routine circumcision, and thus make the procedure more humane.
                Level 1 nursery at a community hospital.
                Eighty healthy, term, newborn male infants scheduled for routine neonatal circumcision.
                Prospective and randomized; double blind and placebo controlled for the study solutions.
                Four statistically similar groups of 20 were studied. The control group included infants circumcised using: a) a rigid plastic restraint board; b) standard DPNB; and c) a pacifier dipped in water to comfort the infant. Each study group differed from the controls in one variable including: 1) using a specially designed, physiologic circumcision restraint chair; 2) pH buffering of lidocaine hydrochloride used for DPNB; and 3) offering a pacifier dipped in a 24% sucrose solution during the DPNB and circumcision. Behavioral observations were recorded and compared for each group starting before the injection of lidocaine hydrochloride and continuing through the completion of the circumcision. Plasma for cortisol levels were collected 30 minutes after the circumcision.
                Neonates circumcised on the new restraint chair showed a significant decrease in distress scores (>50%) compared with the control group on the rigid molded-plastic restraint. The pacifier dipped in sucrose had a distress-reducing effect during both the post-DPNB injection and circumcision periods. The infants who were injected with the buffered lidocaine showed no differences in distress from the controls. The plasma cortisol levels were not significantly affected by any additional technique and were comparable to the levels previously reported.
                When neonatal circumcisions are performed routinely, they should be done as humanely as possible. This study demonstrates that, when used in conjunction with DPNB, a pacifier dipped in 24% sucrose and a more comfortable, padded, and physiologic restraint can be useful in decreasing distress and pain. To assess the effectiveness of sucrose as an analgesic agent during routine immunization injections for infants (age range, 2 weeks to 18 months).
                Double-blind, randomized control trial.
                Ambulatory care clinic of a large tertiary care center.
                A consecutive sample of 285 infants were randomly assigned to one of three treatment groups.
                Subjects received either no intervention or drank 2 mL of sterile water or 2 mL or a 12% sucrose solution 2 minutes before administration of the immunization.
                Infants were videotaped during immunization for later interval recording of pain-induced vocalizations.
                Results were analyzed by using two-way repeated measure analyses of variance. Two-week-old infants who received either the sterile water or sucrose solution cried significantly less than infants who received no intervention (F=5.92,P<.005). For older infants, those who received water or sucrose cried significantly less only if they were administered one injection rather than two injections (F=3.36,P<.05).
                We found that when infants drank sucrose or sterile water, significantly fewer pain vocalizations were produced, but only for 2-week-old infants. For older infants, differences were found only when the number of injections was included in the analysis. We expand on previous findings by demonstrating that both the age of the child and the number of painful exposures can attenuate calming effects. In addition, the results suggest that in the absence of nonnutritive sucking, the actual analgesic effects of sucrose may be nonspecific. Further study is needed of the possible analgesic effects of sucrose. nan The purpose of this randomized clinical trial was to test the efficacy of repeated versus single dose sucrose to decrease pain from routine heel stick procedures in preterm neonates. Infants (n = 48) in the first week of life with a mean gestational age of 31 weeks received 0.05 ml of 24% sucrose solution or sterile water by mouth (1) 2 min prior to actual lancing of the heel; (2) just prior to lancing, and (3) 2 min after lancing. The single-dose group received sucrose for the first dose and water for the second and third dose; the repeated-dose group received sucrose three times, and the placebo group received only water. The Premature Infant Pain Profile (PIPP) scores were obtained for five 30-second blocks from lancing. Both sucrose groups had lower PIPP scores (single sucrose pain scores, 6.8-8.2, p = 0.07; repeated sucrose pain scores, 5.3-6. 2, p < 0.01) than water (pain scores 7.9-9.1), and in the last block, the repeated dose had lower scores than the single dose (6.2 vs. 8. 2, p < 0.05). A double-blind, randomized controlled trial was conducted with infants born <31 weeks of gestational age and recruited within 48 h of life. The infants were randomized to receive up to three doses of 0.1 ml of either 24% sucrose or sterile water (placebo) for every painful procedure during the 1st week of life. The purpose of this study was to test the efficacy of treating all procedural pain with sucrose on overall physiological stability. The hypotheses were that infants who received 24% sucrose for all painful procedures would be less stressed as measured by salivary cortisol, and more physiologically stable as measured by pulse rate variability than those who received placebo. Salivary cortisol was measured before and 30 min after a painful procedure, whereas the pulse rate was continuously recorded, from second to second, from a pulse oximeter. There were no group differences in the cortisol response to a painful stimulus or in pulse rate variability over time. There was, however, a significant correlation between standard deviation of pulse rate and number of doses of sucrose only in the group who received high doses of sucrose.
                Copyright 2004 S. Karger AG, Basel Sucrose is widely used to manage procedural pain in term newborns despite a lack of evidence of its effectiveness for different procedures and infant populations. Our objectives were to evaluate the effectiveness and safety of sucrose in newborns undergoing various medical procedures within 2 days of birth.
                We performed a double-blind, randomized controlled trial. We included newborns (>or= 36 weeks gestation) of diabetic mothers and nondiabetic mothers. Each newborn received 2 mL of a 24%-sucrose or placebo solution before all procedures. We used the Premature Infant Pain Profile to assess pain during intramuscular injection of vitamin K, venipuncture for the newborn screening test and the first 3 heel lances for glucose monitoring (newborns of diabetic mothers only). Scores ranged from from 0 (no pain) to 18 (maximum pain).
                We included 240 newborns (120 from diabetic mothers, 120 from nondiabetic mothers). The overall mean pain score was lower among newborns who received sucrose than among those who received a placebo (mean difference -1.3, 95% confidence interval [CI] -2.0 to -0.6). We found that pain scores during intramuscular injection did not differ significantly between the sucrose and placebo groups for newborns of diabetic or nondiabetic mothers (newborns of nondiabetic mothers: mean difference -1.1, 95% CI -2.4 to 0.2; newborns of diabetic mothers: mean difference -1.0, 95% CI -2.4 to 0.4). During venipuncture, newborns who received sucrose had lower pain scores compared with those who received a placebo (newborns of nondiabetic mothers: mean difference -3.2, 95% CI -4.6 to -1.8; newborns of diabetic mothers: mean difference -2.4, 95% CI -3.8 to -1.0). Among newborns of diabetic mothers, there was no difference in pain during the first 3 heel lances or mean glucose levels between the sucrose and placebo groups (p = 0.94 and p = 0.29 respectively).
                We found a modest reduction of pain in newborns of both diabetic and nondiabetic mothers when sucrose was used for all medical procedures performed in the first 2 days after birth. However, when each procedure was analyzed separately, we found that the effectiveness of sucrose was limited to venipuncture for the newborn screening test. (http://Clinicaltrials.gov trial register no. NCT00213213.). Gavage feeding is required in preterm infants who cannot feed by themselves. Insertion of the feeding tube is painful, and reducing the discomfort in these patients is desirable.
                The aim of this study was to assess pain and discomfort during nasal insertion of a feeding tube, and to evaluate different measures for pain relief.
                We included 24 preterm infants with postmenstrual age 28 to 32 weeks' who were in stable condition. Each infant acted as his or her own control over a 3-week period during which the tube was changed 6 times. On these occasions, 6 different treatment combinations were given in randomized order: pacifier or no pacifier, combined with no fluid, sterile water, or 30% sucrose. Pain and discomfort were assessed by at least 2 independent and experienced observers using a pain assessment tool, the Premature Infant Pain Profile; score range: 0 to 21. In general, scores of 4 to 6 are interpreted as normal or no discomfort; ≥ 12 usually signals significant pain and distress.
                The median Premature Infant Pain Profile score during the procedure was 9 and decreased gradually toward 4 after 5 minutes. The lowest pain score was achieved by combining a pacifier with oral sucrose. Sterile water without a pacifier gave the highest score.
                Insertion of a feeding tube in preterm infants leads to a measurable degree of pain and discomfort, according to the Premature Infant Pain Profile assessment tool. Pain relief was best achieved by combining a pacifier with 30% sucrose. To evaluate the effectiveness of oral sucrose in the prevention of pain-induced crying in preterm infants, a sample of 28 healthy neonates (15M, 13F; gestational age at procedure less than 37 weeks) who were having routine blood drawn by arm venipuncture was studied. Infants were randomly allocated to receive by mouth, using a syringe, 2 ml of one of three solutions: spring water (group W) and sucrose 12 and 24% w/v (groups S12 and S24, respectively), all in water vehicle. After 2 min, while awake, arm venipuncture was performed and duration of crying was measured. The time spent crying was reduced in the group treated with the sweetest solution (S24, n = 8, mean = 19.1 s). No difference was observed between the S12 group (n = 8, mean = 63.1 s) and W group (n = 12, mean = 72.9 s). Physiological measurements were recorded at different time points to evaluate excessive basal and procedural distress. To understand how the 'caregiving context' could affect responses to procedural pain, the authors sought to determine whether (1) the combined effects of sweet taste and holding (caregiving contact) were greater than the effects of either alone, (2) any combined effects were additive or interactive, and (3) the interventions had similar effects on behavioral (crying and facial activity) and physiological (heart rate, vagal tone) responses to the heel-stick procedure in newborn infants in a randomized two-factorial intervention trial. Eighty-five normally developing newborn infants were studied with a mean gestational age of 39.4 weeks on the 2nd or 3rd day of life. Infants were randomized in blocks of eight to receive (1) no holding and water taste (control participants), (2) no holding and sucrose taste (sucrose group), (3) holding and water taste (holding group), or (4) holding and sucrose taste (holding and sucrose group). Crying was reduced significantly by taste and holding, and the interventions combined additively. Facial activity was only significantly reduced by holding. For physiological measures, the interventions interacted with each other and preintervention levels to reduce heart rate and lower vagal tone more during the procedure in infants in whom heart rate and vagal tone were higher before intervention. Consequently, sweet taste and holding interventions combined in complex ways when acting on different behavioral and physiological response systems to modify stressful pain experiences. The results suggest that providing a caregiving context when painful procedures are performed may be a simple and practical method of reducing pain experience in infants, and that no one measure captures these effects. Feeding and carrying have been interventions used by caregivers throughout history in relieving distress in infants. Recent studies on the food substance sucrose have elucidated the comforting effect of the taste component of feeding while studies of rocking have examined the comforting effect of the vestibular component of carrying. The purpose of this study was to determine the effectiveness of sucrose and simulated rocking alone and in combination on diminishing pain response in preterm neonates undergoing routine heelstick procedure in the neonatal intensive care unit (NICU). Preterm infants (n = 85) between 25-34 weeks post-conceptual age (PCA) and 2-10 days postnatal age (PNA) were randomly assigned to one of four conditions for routine heelstick procedure. The conditions were (1) sucrose alone: 0.05 ml of 24% sucrose was placed on the anterior surface of the tongue just prior to the lancing of the heel; (2) simulated rocking alone: 15 min prior to and during the heelstick procedure, the infant was swaddled and put on an oscillating mattress; (3) combination of sucrose and simulated rocking; and (4) placebo: 0.05 ml sterile water administered just prior to heelstick. Physiological (heart rate) and behavioural (facial actions) responses from baseline across 90 s following heelstick were scored second-to-second. Facial actions were analysed with repeated measures MANCOVA and heart rate with repeated measures ANCOVA. Behavioural state and gestational age were covariates. The groups that received sucrose alone or in combination with simulated rocking showed less facial actions indicative of pain than the rocking alone or control group. The addition of rocking to the sucrose condition tended to further blunt the facial expression of pain, but this enhancement did not reach a significant level. Heart rate was not decreased by any intervention compared to the control condition. Although the simulated rocking did promote quiet sleep, which has been reported in earlier studies to blunt pain response, there was no difference between simulated rocking and control groups in either facial expressions indicative of pain or heart rate. The implication of these results is that sucrose, but not simulated rocking may be a means of diminishing pain from minor procedures in preterm infants. Further research is needed on the use of sucrose for more than one procedure as well as examining the contact component of natural rocking, as opposed to simulated rocking. To evaluate the pain in healthy newborns requiring blood test by a heel-prick procedure and compare different pain management methods.
                We studied 150 term infants, in three randomised groups, from the Maternity Unit of our Hospital for a period of three months. The first group of 50 newborns, received no specific analgesic intervention during blood tests, except our usual nursing intervention ("facilitated tucking"). The second and third group (50 newborns), received non-nutritive sucking-placebo and non-nutritive sucking-24% sucrose respectively.
                In the control group, the average score on the scale of discomfort was 3.92, moderate pain, causing a crying time of 51.72 seconds; the group receiving a non-nutritive sucking-placeboscored 2.1, slight pain, 10.68 seconds crying, while the group receiving non-nutritive sucking-24 % sucrose, expressed a level of discomfort of 1.5 points, slight, with an average crying time of 10.70 seconds. The comparative results between the control group and groups of non-nutritive sucking on placebo and 24% sucrose, both showed significant differences in the scores of the scale of discomfort, as well as in the time crying (p < 0.001). The comparative analysis between groups of non-nutritive sucking sucrose and placebo showed no significant differences.
                The blood test by heel lance represents a painful procedure of moderate intensity capable of analgesic treatment. A proper nursing method, along with a complement of non-nutritive sucking during extraction, significantly decreases the discomfort and crying, it being unnecessary to consider other analgesics. To evaluate the effects of different sucrose concentrations on measures of neonatal pain.
                Randomised, double blind, placebo controlled trial of sterile water (control) or one of three solutions of sucrose--namely, 12.5%, 25%, and 50% wt/vol.
                Postnatal ward.
                60 healthy infants of gestational age 37-42 weeks and postnatal age 1-6 days randomised to receive 2 ml of one of the four solutions on to the tongue two minutes before heel prick sampling for serum bilirubin concentrations.
                Duration of crying over the first three minutes after heel prick.
                There was a significant reduction in overall crying time and heart rate after three minutes in the babies given 50% sucrose as compared with controls. This was maximal one minute after heel prick in the 50% sucrose group and became statistically significant in the 25% sucrose group at two minutes. There was a significant trend for a reduction in crying time with increasing concentrations of sucrose over the first three minutes.
                Concentrated sucrose solution seems to reduce crying and the autonomic effects of a painful procedure in healthy normal babies. Sucrose may be a useful and safe analgesic for minor procedures in neonates. The aim of this study was to compare the analgesic effect of 2 ml 25% sucrose and human milk in a group of healthy term newborns. Healthy infants (n = 102) were randomly allocated to receive one of three solutions (sucrose, human milk, sterile water) 2 min prior to taking a heel prick blood sample. The median values of crying time, recovery time and percentage change in heart rate at 1, 2 and 3 min were recorded in response to the heel prick. Median crying times were 36, 52, and 62 s in the sucrose, placebo and human milk groups, respectively (P = 0.0009). In the sucrose group, there was a significant reduction in crying time compared to human milk and placebo groups. Similarly, the median recovery time in the sucrose group (72 s) was shorter than that in the human milk (112 s) and placebo groups (124 s) (P = 0.004). The percentage change in heart rate at 1, 2 and 3 min was also significantly lower in the sucrose group (P = 0.008, P = 0.01, P = 0.002 at 1, 2, and 3 min respectively).
                The orosensorial antinociceptive effect of human milk is not as effective as an analgesic as a 25% sucrose solution. In this study, we aimed to compare the analgesic effect of 30% sucrose and 10% and 30% glucose in a group of healthy term newborns. A total of 113 infants whose heels were pricked for the guthrie test were included in the study. The babies were randomized into 4 groups, receiving 2 ml of 30% sucrose, 10% glucose, 30% glucose, or distilled water. Response to pain was assessed by mean crying time, recovery time, maximum heart rate, and percent change in heart rate at 1, 2, and 3 minutes. Mean crying times were 60, 102, 95, and 105 seconds in the sucrose, 10% glucose, 30% glucose, and placebo groups, respectively (P =.02). Although mean recovery time was shorter in the sucrose group (102 seconds), there was neither a significant difference between the groups (10% glucose, 121 seconds; 30% glucose, 109 seconds; control group, 132 seconds [P =.09]), Nor was there a difference in maximum heart rate and percent change in heart rate at 1, 2, and 3 minutes after heel prick (P =.14, P =.05, P =.53 For the first, second, and third minutes, respectively ). However, a statistically borderline difference existed at the end of 2 minutes favoring sucrose (P =.05). We conclude that 30% sucrose is superior to 10% and 30% glucose solutions in relieving pain, showing its primary effect in crying time. As glucose solutions are readily available in neonatal intensive care units and easier to use in routine practice, further trials are needed to evaluate the antinociceptive effect of glucose when combined with other nonpharmacologic methods. To determine the efficacy of sucrose analgesia for procedural pain during the first week of life in preterm neonates in neonatal intensive care units on enhancing later clinical outcomes.
                A total of 107 preterm neonates who were born at <31 weeks' postconceptional age (PCA) entered this double-blind, randomized, controlled trial within 48 hours of birth at 3 level III university-affiliated neonatal intensive care units in Canada, and 103 completed the study. Sucrose (0.1 mL of 24%) or sterile water was administered orally up to 3 times, 2 minutes apart, for every invasive procedure during a 7-day period. Motor development and vigor, and alertness and orientation components of the Neurobehavioral Assessment of the Preterm Infant were measured at 32, 36, and 40 weeks' PCA; Score for Neonatal Acute Physiology was measured on the last day of intervention; and Neuro-Biological Risk Score (NBRS) was measured at 2 weeks of age and at discharge. Primary analyses of covariance were applied for each outcome to compare group differences followed by secondary analyses using standard linear regression within each group to determine predictors of outcomes.
                Although there were no differences between the groups on any outcomes, there were significant dose-related effects within each group. In the sucrose group only, higher number of doses of sucrose predicted lower scores on motor development and vigor, and alertness and orientation at 36 weeks', lower motor development and vigor at 40 weeks', and higher NBRS at 2 weeks' postnatal age. Higher number of invasive procedures was predictive of higher NBRS both times in the water group.
                Repeated use of sucrose analgesia in infants <31 weeks' PCA may put infants at risk for poorer neurobehavioral development and physiologic outcomes. Additional study is needed to determine the most appropriate age and duration of sucrose analgesia in preterm infants. Infants undergoing eye exams to screen for retinopathy of prematurity (ROP) demonstrate physiologic and behavioral manifestations of pain and distress. Oral sucrose has analgesic properties that might reduce these effects.
                To determine the efficacy of oral sucrose in reducing the pain/distress of eye exams for ROP.
                A total of 32 infants about to undergo ROP screening exams received either oral sucrose [S] (N=16) or sterile water [C] (N=16) in a randomized, prospective and blinded fashion. Outcome measures included HR, RR, O(2) saturation, BP, pain (premature infant pain profile) and percent of time spent crying during the eye exam.
                The groups were similar in GA (weeks) (28+/-1.6), BW (kg) (1.04+/-0.26), postnatal age (days) 50.8+/-20.3, and study weight (kg) 1.88+/-0.40). Both groups demonstrated significant increases in HR, BP, and pain score in response to the exam. Infants in both groups spent the majority of time actively crying during the exam ([S] 53+/-35% vs [C] 63+/-31%. Infants receiving [S] showed a small but significant drop in O(2) saturation. No significant differences were seen between groups in physiologic or behavioral responses to the eye exam.
                Oral [S] was not effective in reducing pain/distress from the ROP screening exam. Alternative strategies should be considered to achieve adequate pain relief. To examine the efficacy of pacifiers and sugar, alone and in combination, for pain management in neonates.
                An experimental design examined pain responses of 84 newborns undergoing heelstick. They were randomly assigned to one of four groups: (a) water-moistened pacifier, (b) sugar-coated pacifier, (c) 2 cc of a 12% oral sucrose solution, or (d) control. Pain measures were duration of cry, vagal tone, and salivary cortisol.
                Multivariate analysis of variance (MANOVA) revealed that the sugar-coated pacifier group cried significantly less than the water-moistened pacifier and control groups. Repeated measures analysis of variance (ANOVA) revealed that the sugar-coated pacifier group demonstrated significantly lower vagal tone during heelstick than the oral sucrose solution and control groups. This difference between the sugar-coated pacifier and control groups persevered for 15 minutes after heelstick.
                Offering a sugar coated pacifier during heelstick in healthy neonates reduces pain behaviors more effectively than a water-moistened pacifier, 2 cc of a 12% sucrose solution, or no intervention. Preterm neonates undergo numerous painful procedures in the neonatal intensive care unit (NICU). Sucrose, with and without pacifiers, is effective and safe for relieving pain from single painful events. However, repeated use of sucrose for multiple painful procedures has not been adequately evaluated. The study objectives were to: 1) determine the efficacy and safety of consistent management of repeated procedural pain with sucrose; and 2) explore the impact of consistent pain management on clinical outcomes and neurobiological risk status.
                Sixty-six preterm infants were randomized to receive standard care (positioning and swaddling; n = 21), sterile water plus pacifier (n = 23), or 24% sucrose plus pacifier (n = 22) prior to all painful procedures in the NICU during the first 28 days of life. Also, at a routine heel lance at 7, 14, 21, and 28 days of life, data were collected to determine efficacy and immediate and long-term adverse events. Data on clinical outcomes and neurobiological risk status were collected at 28 days or NICU discharge.
                There was no intervention by time interaction (P = 0.60). There was a significant main effect of intervention (P = 0.03) between the sucrose plus pacifier group, and the standard care group (P = 0.01), but there was no main effect of time (P = 0.72). No group differences existed for adverse events, clinical outcomes, or neurobiological risk status.
                Consistent management of painful procedures with sucrose plus pacifier was effective and safe for preterm neonates during their stay in the NICU. Further exploration of consistent pain management with sucrose on clinical, developmental, and neurobiological outcomes is required. The goal of this study was to compare the analgesic effect of sucrose with that of the combination of sucrose and the local anesthetic cream EMLA during venipuncture in preterm neonates.
                This randomized, double-blind prospective study included infants younger than 37 weeks' gestational age during 1 routine venipuncture for blood sampling. Each child randomly received either sucrose plus application of a placebo cream (S group) or sucrose plus EMLA cream (S+E group) before venipuncture. Venipuncture-induced pain was assessed through videotapes of the procedures by using the Douleur Aiguë Nouveau-né (DAN) behavioral scale. Pain was assessed at 2 phases: during venipuncture (from needle introduction to its removal) and during the recovery period (30 seconds after needle removal). Pain scores over time and between treatments were compared by using repeated-measures analysis of variance.
                The study included 76 children (37 in the S group, 39 in the S+E group). Mean (SD) DAN pain scores for the S group and the S+E group were 7.7 (2.1) and 6.4 (2.5), respectively, during venipuncture and 7.1 (2.8) and 5.7 (3.3) during the postinjection period. A significant time and treatment effect in favor of the S+E group was observed.
                The combination of sucrose and EMLA cream revealed a higher analgesic effect than sucrose alone during venipuncture in these preterm infants.
                Copyright © 2011 by the American Academy of Pediatrics.