Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus -Haemophilus influenzae type b conjugate and hepatitis B vaccines in infants from birth to six months of age Breastfeeding and pain relief in full-term neonates during immunization injections: a clinical randomized trial Addressing Parental Concerns About Pain During Childhood Vaccination: Is There Enough Time to Include Pain Management in the Ambulatory Setting? Suckling- and sucrose-induced analgesia in human newborns Milk-induced hypoalgesia in human newborns. Effects of acetaminophen on adverse effects of influenza vaccination in health care workers. Interventions to reduce pain during vaccination in infancy. Effects of Prophylactic and Therapeutic Paracetamol Treatment during Vaccination on Hepatitis B Antibody Levels in Adults: Two Open-Label, Randomized Controlled Trials Comparison of analgesic effect of direct breastfeeding, oral 25% dextrose solution and placebo during 1st DPT vaccination in healthy term infants: A randomized, placebo controlled trial Effective Analgesia Using Physical Interventions for Infant Immunizations Vaccine immune response and side effects with the use of acetaminophen with influenza vaccine. Topical 4% Amethocaine Gel Reduces the Pain of Subcutaneous Measles-Mumps-Rubella Vaccination The use of a topical refrigerant anesthetic to reduce injection pain in children. Oral glucose as an analgesic to reduce infant distress following immunization at the age of 3, 5 and 12 months. Sucrose and Warmth for Analgesia in Healthy Newborns: An RCT The use of breast-feeding for pain relief during neonatal immunization injections. Randomized controlled trial of topical EMLA and breastfeeding for reducing pain during wDPT vaccination CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials Efficacy of Parental Application of Eutectic Mixture of Local Anesthetics for Intravenous Insertion Vapocoolant spray is equally effective as EMLA cream in reducing immunization pain in school-aged children. Use of lidocaine-prilocaine cream for vaccination pain in infants. Oral sucrose and a pacifier for pain relief during simple procedures in preterm infants: a randomized controlled trial. Analgesic Properties of Oral Sucrose During Routine Immunizations at 2 and 4 Months of Age Nonnutritive sucking and oral sucrose relieve neonatal pain during intramuscular injection of hepatitis vaccine. Lidocaine-prilocaine patch decreases the pain associated with the subcutaneous administration of measles-mumps-rubella vaccine but does not adversely affect the antibody response. [The EMLA cream versus placebo in MMR vaccination of older children in general practice]. EMLA® cream: A pain-relieving strategy for childhood vaccination Immunogenicity and adverse reactions of influenza vaccination in elderly patients given acetaminophen or placebo. Intra-Oral Administration of Sweet-Tasting Substances and Infants’ Crying Response to Immunization: A Randomized, Placebo-Controlled Trial Sucrose as an analgesic agent for infants during immunization injections. Sucrose decreases infant biobehavioral pain response to immunizations: a randomized controlled trial. A randomized double‐blind, placebo‐controlled trial of the EMLA® patch for the reduction of pain associated with intramuscular injection in four to six‐year‐old children Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials Comparison of EMLA cream with rattles on reducing immunization pain in four months infants. A randomized controlled trial of analgesia during vaccination in adults. A local reaction at or near injection site: case definition and guidelines for collection, analysis, and presentation of immunization safety data. The effect of breastfeeding, oral sucrose and combination of oral sucrose and breastfeeding in infant's pain relief during vaccination Topical ibuprofen for skin analgesia prior to venepuncture A Randomized Controlled Trial of Vapocoolant for Pediatric Immunization Distress Relief Oral sucrose administration to reduce pain response during immunization in 16–19-month infants: a randomized, placebo-controlled trial Skin-to-Skin Contact and/or Oral 25% Dextrose for Procedural Pain Relief for Term Newborn Infants Effects of a skin refrigerant/anesthetic and age on the pain responses of infants receiving immunizations. Topical vapocoolant quickly and effectively reduces vaccine-associated pain: results of a randomized, single-blinded, placebo-controlled study. EMLA® cream and oral glucose for immunization pain in 3-month-old infants “Sucrose Analgesia” and Diphtheria‐Tetanus-Pertussis Immunizations at 2 and 4 Months The effects of a pacifying stimulus on behavioral and adrenocortical responses to circumcision in the newborn. A double-blind randomised controlled trial of 25% oral glucose for pain relief in 2-month old infants undergoing immunisation.
Background . Topical lidocaine-prilocaine ( EMLA ) effectively decreases the pain associated with minor procedures including immunization , although the effect on the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus -Haemophilus influenzae type b conjugate ( DTaP-IPV-Hib ) and hepatitis B vaccines has not been assessed . Objective . To measure the antibody response to DTaP-IPV-Hib and hepatitis B vaccines ; to measure pain reduction associated with the use of the lidocaine-prilocaine ( EMLA ) patch ; and to assess safety by comparing adverse reactions . Participants and setting . One hundred nine healthy 6-month-old infants ( Part A of study ) and 56 healthy infants birth to 2 months of age ( Part B of study ) undergoing primary immunization with DTaP-IPV-Hib and hepatitis B vaccines in an ambulatory setting . Design and interventions . Two center , r and omized , double blind , controlled trial of EMLA patch or placebo before DTaP-IPV-Hib and hepatitis B immunization . Antibody titers measured at 0 to 2 , 6 and 7 months . Outcome measures . The primary outcome measure was the antibody response to diphtheria , tetanus , pertussis antigens , Haemophilus influenzae type b and hepatitis B by enzyme immunoassay ; and poliovirus 1 , 2 and 3 by neutralization . The secondary outcomes were pain scores by the Modified Behavioral Pain Scale and drug- and vaccine-associated adverse events collected with a parent diary and structured question naire . Results . There was no difference in the antibody response between the EMLA- and placebo-treated groups as assessed by geometric mean antibody titers , rates of seroconversion or the proportion of participants achieving protective or positive antibody titers postimmunization . At the 6-month visit , EMLA recipients had less pain after immunization ( total pain score , 6.75 vs. 7.35;P = 0.005 ; pain score increase , 3.99 vs. 4.74;P = 0.004 ) than did placebo recipients . Skin pallor and erythema at the patch application site were more frequently reported after EMLA use . Rates of vaccine-associated adverse events were similar in the two groups . Conclusions . The EMLA patch has no adverse effect on the antibody response to the vaccine antigens , is effective in reducing pain associated with DTaP-IPV-Hib and hepatitis B immunizations and does not result in any significant or unexpected adverse reactions Background The aim of this study was to examine the effect of breastfeeding on pain relief in full-term neonates during injection of hepatitis B vaccine . Methods This was a r and omized clinical trial . A sample of full-term neonates was r and omly allocated into two groups : the experimental group and the control group . Neonates in the experimental group were breastfed two minutes before , during , and after the hepatitis B immunization and the control group were held in mothers ’ arms but not fed .  Pain was assessed using the Douleur Aiguë du Nouveau-né ( DAN ) scale measuring facial expressions , limb movements and vocal expressions . The assessment s were carried out after hepatitis B immunization . Results One hundred thirty healthy full-term neonates were studied ( 65 in the experimental group and 65 in the control group ) . Gestational age , birth weight , Apgar score and gender did not differ between the two groups . The mean total pain score as measured by the DAN scale was 3.52 ( SD = 1.37 ) for the experimental group and it was 6.78 ( SD = 1.69 ) for the controls indicating a significant lower pain score for the experimental group ( P<0.001 ) . Also , there were significant differences for the three measures of DAN scale that are facial expressions , limb movements and vocal expression , between the two study groups ( P<0.001 ) . Conclusion The findings confirm that breastfeeding reduces pain and is effective way for pain relief during hepatitis B vaccine injection . Trial registration I RCT Objective : Pain from vaccine injections remains undertreated , despite the availability of numerous pain-relieving strategies . Healthcare providers report lack of time within current office workflows as a major barrier to routine pain management . The objective was to document the total time involved in outpatient vaccine appointments to test the hypothesis that offering pain-relieving strategies can be practically implemented when considering the element of time to vaccine injection . Patients and Methods : Prospect i ve naturalistic study in 8 urban outpatient primary care clinics ( 4 pediatric and 4 family practice ) in Toronto . For 48 to 59 consecutive childhood vaccination appointments at each site , child waiting time from clinic arrival until first vaccine injection was tracked . Results : Altogether , 405 vaccine appointments were included . The median age of the child undergoing vaccination was 12 months . The mean ( SD ) time from clinic arrival until first vaccine injection was 41.6 minutes ( 20.9 ) , with a range of 7 to 132 minutes . Linear regression identified a significant ( P<0.05 ) difference according to clinic [ ranging from 19.4 min ( 6.5 ) to 57.5 min ( 20.2 ) ] and number of family members in the appointment [ ranging from 40.6 min ( 21.0 ) for an appointment in the index child only to 50 min ( 14.3 ) for an appointment in the index child and 2 other family members ] . Conclusions : Contrary to healthcare provider perceptions , the timing of outpatient childhood vaccine appointments allows for the inclusion of pain management interventions . Efforts should now focus on educating healthcare providers and parents about the value of pain management and how to implement evidence -based strategies 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 OBJECTIVE To determine whether milk and its components reduce  crying  in newborns during and after blood collection for phenylketonuria evaluation . METHODOLOGY 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 . RESULTS 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 . CONCLUSION 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 OBJECTIVE To evaluate the effects of acetaminophen on the incidence of adverse effects to , and the immunogenicity of , whole-virus influenza vaccine in health care workers . DESIGN Prospect i ve , r and omized , double-blind placebo-controlled trial . SETTING Health Sciences Centre , an acute care teaching hospital in Winnipeg . PARTICIPANTS Of 474 hospital personnel who agreed to undergo influenza vaccination during the 1990 - 91 season 262 volunteered to participate in the study . INTERVENTIONS A dose of 0.5 mL of inactivated trivalent whole-virus influenza vaccine was injected into the deltoid muscle . Volunteers were r and omly assigned to ingest two capsules of acetaminophen in a half dose ( 162.5 mg per capsule ) or a full dose ( 325 mg per capsule ) or two identical placebo capsules . Capsules were to be taken at vaccination and at 4 , 8 and 12 hours afterward . Subjects were asked to answer questions regarding six symptoms in a diary for the 3 days after vaccination and to record their ingestion of the study medication . MAIN OUTCOME MEASURES Incidence of local ( sore arm ) and systemic ( headache , fever , muscle ache , nausea and diarrhea ) side effects as well as serum titres of hemagglutination inhibition ( HAI ) antibody to vaccine antigens before vaccination and 2 weeks and 6 months afterward . RESULTS A total of 87 , 87 and 88 subjects received the half dose , full dose and placebo respectively ; 96 % returned the diaries , 83 % ingested all four doses of medication , and 87 % volunteered all blood sample s. Compared with the placebo group the incidence of sore arm was 25 % to 28 % lower in the half-dose and full-dose groups respectively at 24 hours after vaccination , and the rate of nausea was 90 % lower in the full-dose group . The HAI titres were similar among the groups at the three test times . CONCLUSIONS The full dose of acetaminophen significantly reduced the incidence of sore arm and nausea without affecting the antibody response . Acetaminophen use may increase the acceptance of influenza vaccine by health care workers in whom concern about side effects is an impediment to vaccination OBJECTIVE To investigate interventions that affect pain reduction during vaccination in infants and children attending a well-child unit . STUDY DESIGN A consecutive sample of 243 children between age 0 and 48 months receiving their routine vaccinations was r and omly assigned to 1 of the study groups . A total of 158 infants under age 6 months were r and omly assigned to breast-feeding or no breast-feeding during immunization , and 85 children age 6 to 48 months were r and omly assigned to receive 12 % sucrose solution , lidocaine-prilocaine cream , or no intervention . All children were evaluated for crying time and pain score by a pediatrician using the Neonatal Infant Pain Scale ( NIPS ) for those under age 12 months and the Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) for those over age 12 months . RESULTS Breast-feeding in infants under age 6 months and use of sucrose or lidocaine-prilocaine in children age 6 to 48 months significantly reduced crying time and pain scores compared with controls . No difference in outcome was seen between the sucrose and lidocaine-prilocaine treatment groups . CONCLUSIONS Here we exp and on previous findings by demonstrating that breast-feeding may have an analgesic effect up to age 6 months and that in older children , both sucrose and lidocaine-prilocaine reduce vaccination pain Worldwide , paracetamol is administered as a remedy for complaints that occur after vaccination . Recently published results indicate that paracetamol inhibits the vaccination response in infants when given prior to vaccination . The goal of this study was to establish whether paracetamol exerts similar effects in young adults . In addition , the effect of timing of paracetamol intake was investigated . In two r and omized , controlled , open-label studies 496 healthy young adults were r and omly assigned to three groups . The study groups received paracetamol for 24 hours starting at the time of ( prophylactic use ) - or 6 hours after ( therapeutic use ) the primary ( 0 month ) and first booster ( 1 month ) hepatitis B vaccination . The control group received no paracetamol . None of the participants used paracetamol around the second booster ( 6 months ) vaccination . Anti-HBs levels were measured prior to and one month after the second booster vaccination on ADVIA Centaur XP . One month after the second booster vaccination , the anti-HBs level in the prophylactic paracetamol group was significantly lower ( p = 0.048 ) than the level in the control group ( 4257 mIU/mL vs. 5768 mIU/mL ) . The anti-HBs level in the therapeutic paracetamol group ( 4958 mIU/mL ) was not different ( p = 0.34 ) from the level in the control group . Only prophylactic paracetamol treatment , and not therapeutic treatment , during vaccination has a negative influence on the antibody concentration after hepatitis B vaccination in adults . These findings prompt to consider therapeutic instead of prophylactic treatment to ensure maximal vaccination efficacy and retain the possibility to treat pain and fever after vaccination . Trial Registration Controlled-Trials.com IS RCT Objective To compare analgesic effect of direct breast feeding , 25 % dextrose solution and placebo as we give 1st intramuscular whole cell DPT injection to 6week — 3month old infants . Design R and omized , placebo controlled trial . Setting Immunization clinic of Department of Pediatrics , LLRM Medical College . Participants Infants coming for their 1st DPT vaccination were r and omized in to three groups of 40 each . Outcome measures The primary outcome variable was the duration of cry after vaccination . Secondary outcome variables were Modified Facial Coding Score ( MFCS ) and latency of onset of cry . Results 120 babies were equally enrolled in breast feed group , 25 % dextrose fed group and distilled water fed group .  Median ( interquartile range ) of duration of cry was significantly lower in breast fed ( 33.5 ( 17–54 ) seconds ) and 25 % dextrose fed babies ( 47.5 ( 31–67.5 ) seconds ) as compared to babies given distilled water ( 80.5 ( 33.5–119.5 ) seconds ) ( P<0.001 ) . MFCS at 1 min and 3 min was significantly lower in direct breast fed and dextrose fed babies . Conclusions Direct breastfeeding and 25 % dextrose act as analgesic in young infants undergoing DPT vaccination in young infants less than 3 month of age BACKGROUND : To measure the analgesic effectiveness of the 5 S ’s ( swaddling , side/stomach position , shushing , swinging , and sucking ) alone and combined with sucrose , during routine immunizations at 2 and 4 months . METHODS : We conducted a prospect i ve , r and omized , placebo-controlled trial with 2- and 4-month-old infants during well-child visits . Patients were assigned into 4 groups ( 2 × 2 ) receiving either 2 mL of water or 2 mL of 24 % oral sucrose and then either st and ard-of-care comfort measures by parents or intervention with the 5 S ’s immediately postvaccination .  The Modified Riley Pain Score was used to score the infants ’ pain at 15-second intervals for 2 minutes , then every 30 seconds up to 5 minutes postvaccination . Repeated- measures analysis of variance examined between group differences and within-subject variability of treatment effect on overall pain scores and length of crying . RESULTS : Two hundred thirty infants were enrolled . Results revealed significantly different mean pain scores between study groups with the exception of the 5S ’s and 5S ’s with sucrose groups . These 2 groups had lower similar mean scores over time , followed by sucrose alone , then control . The same trend was found with the proportion of children crying as with the mean pain score outcome measure . CONCLUSIONS : Physical intervention of the 5 S ’s ( swaddling , side/stomach position , shushing , swinging , and sucking ) provided decreased pain scores on a vali date d pain scale and decreased crying time among 2- and 4-month-old infants during routine vaccinations . The use of 5S ’s did not differ from 5S ’s and sucrose The purpose of this study was to determine whether acetaminophen impairs the immune response to  influenza vaccine . Influenza vaccine is an under-utilized preventive measure , partly because of the unfounded perception that fever and myalgias frequently follow vaccination . While acetaminophen may decrease these infrequent side effects , it may also alter the immune response to vaccination . We compare the effect of acetaminophen with placebo on the humoral immune response to the 1991 - 1992 commercially available influenza vaccine . We studied 60 healthy , elderly subjects from a geriatric clinic and 20 infirm , elderly subjects from a nursing home . The subjects were r and omly assigned to receive placebo or acetaminophen ( 1,000 mg every 6 h ) for 2 days . Acetaminophen did not depress or enhance the immune development of serum hemagglutination inhibition antibody to the three vaccine antigens . The systemic side effects of fever and myalgia were uncommon in both groups . The healthy elderly subjects mounted a significantly better immune response to the influenza virus A/Taiwan/1/86 ( H1N1 ) vaccine strain than did the infirm elderly subjects ( geometric mean titer , 115 versus 51 ; P = 0.003 ) . The functional activity score obtained by using the chronic healthy evaluation component of the Acute Physiology and Chronic Health Evaluation system could be used to distinguish the healthy from the infirm elderly ( scores of 1.27 versus 3.75 , P < 0.001 ) . Acetaminophen neither depressed nor enhanced the serum antibody response to the vaccine in the healthy and infirm elderly subjects studied Objectives . Ametop gel ( 4 % amethocaine ) is a relatively new topical anesthetic that produces anesthesia within 30 to 45 minutes and therefore may be appropriate for use in busy outpatient setting s. The objective of this study was to assess the efficacy and safety of 4 % amethocaine in reducing the pain of subcutaneous measles-mumps-rubella vaccination in 1-year-old infants . Methods .A double-blind , r and omized , placebo-controlled trial was conducted in pediatric outpatient clinics . Results .A total of 120 infants participated in the study ; 60 were followed up for assessment of antibody titers after 1 month . Either 1 g of amethocaine or placebo was applied for 30 minutes before vaccination . The Modified Behavioral Pain Scale was used to assess pain ; the mean ( st and ard deviation ) pain scores for the amethocaine group ( n = 61 ) was 1.5 ( 1.6 ) versus 2.3 ( 2.2 ) for the placebo group ( n = 59 ) . The rate of vaccination success ( 88 % and 87 % ) was not different between treatment groups . Conclusions .4 % Amethocaine significantly reduces the pain of measles-mumps-rubella vaccination in infants when compared with placebo and does not seem to interfere with subsequent development of protective antibody levels . Because of its relatively short application time ( 30 minutes ) , 4 % amethocaine may be suitable for busy clinics and emergency departments Early childhood experiences with painful injections may lead to anxiety and fear . These reactions need not develop if steps are taken to reduce the pain associated with injections . The purpose of this study was to assess the efficacy of a refrigerant topical anesthetic in reducing injection pain in preschool children experiencing routine diphtheria-pertussis-tetanus ( DPT ) immunizations . This double-blind placebo-controlled study was conducted in community health clinics in conjunction with ongoing immunization programs . Ninety subjects , aged 4 - 5.5 years , were r and omly assigned to one of three groups : ( a ) refrigerant topical anesthetic ; ( b ) placebo topical spray ; and ( c ) no-spray control .  Pain was measured subjectively using a four-point visual analogue scale . Both the refrigerant topical anesthetic spray and the placebo spray significantly reduced injection pain . Age was found to be an important factor influencing pain response in this study . Parental anxiety was not a significant factor influencing pain response . In addition , parents were not good at predicting their child 's pain . The results of the study support the use of an intervention , such as refrigerant topical anesthetic , as a practical , simple , and effective treatment strategy for reduction of short-term painful procedures like injections AIM To evaluate oral glucose as an analgesic to reduce  infant distress after immunization during the first year of life and to investigate if these effects change during this period . METHODS A prospect i ve controlled trial of the effectiveness of glucose on crying response to immunizations at 3 , 5 and 12 months of age . A total of 110 infants were r and omized to receive 2 mL of 30 % glucose or water . The same solution was given at 3 , 5 and 12 months . Crying was registered from onset of the injection up to 120 seconds . Infanrix Polio Hib was administered intra-muscular in the thigh . Observation nurse and parents were blind to the nature of the solution . RESULTS Administration of glucose reduced the mean crying time by 22 % at 3 months , 62 % at 5 months and 52 % at 12 months . The difference was significant at 5 and at 12 months . In the water group , there was a significant correlation between the children who cried at 3 months and who subsequently cried at 5 and 12 months . No correlations were found in the glucose group . CONCLUSION Sweet solution can be used as a simple and safe method to reduce the distress following immunization in infants up to 12 months BACKGROUND AND OBJECTIVE : Increasing data suggest that neonatal pain has long-term consequences . Nonpharmacologic techniques ( sucrose taste , pacifier suckling , breastfeeding ) are effective and now widely used to combat minor neonatal pain . This study examined the analgesic effect of sucrose combined with radiant warmth compared with the taste of sucrose alone during a painful procedure in healthy full-term newborns . METHODS : A r and omized , controlled trial included 29 healthy , full-term newborns born at the University of Chicago Hospital . Both groups of infants were given 1.0 mL of 25 % sucrose solution 2 minutes before the vaccination , and 1 group additionally was given radiant warmth from an infant warmer before the vaccination . We assessed pain by comparing differences in cry , grimace , heart rate variability ( ie , respiratory sinus arrhythmia ) , and heart rate between the groups . RESULTS : The sucrose plus warmer group cried and grimaced for 50 % less time after the vaccination than the sucrose alone group ( P < .05 , respectively ) . The sucrose plus warmer group had lower heart rate and heart rate variability ( ie , respiratory sinus arrhythmia ) responses compared with the sucrose alone group ( P < .01 ) , reflecting a greater ability to physiologically regulate in response to the painful vaccination . CONCLUSIONS : The combination of sucrose and radiant warmth is an effective analgesic in newborns and reduces pain better than sucrose alone . The ready availability of this practical nonpharmacologic technique has the potential to reduce the burden of newborn pain The objective of this study was to examine the pain-relieving effect of breast-feeding during immunization injections in healthy neonates . Sixty-six healthy infants returning to a clinic for their second- , third- , or fourth-month immunization with intramuscular diphtheria , tetanus , and pertussis  were r and omized to be breast-fed before , during , and after the injection or to be given the injection according to routine clinic procedure ( no breast-feeding ) . To assess the pain responses of the neonates during and after immunization , we noted their heart rates , oxygen saturation levels , and length of crying . The crying time was shorter in the experimental ( breast-feeding ) group ( M + /- SD duration , 35.85 + /- 40.11 seconds ) than in the control group ( M + /- SD duration , 76.24 + /- 49.61 seconds ; p = .001 ) . The heart rate and oxygen saturation levels were almost the same in both groups . We concluded that breast-feeding , maternal holding , and skin-to-skin contact significantly reduced crying in infants receiving an immunization injection for diphtheria , tetanus , and pertussis The primary objective was to evaluate the analgesic effect of a eutectic mixture of local anesthetics ( EMLA ) during whole cell DPT vaccination . The secondary objective was to evaluate if the analgesic effect of EMLA was synergistic to breastfeeding . A r and omized , placebo-controlled trial was done to include infants of up to 3 months of age who came for their first DPT vaccination . The outcome variables were duration of cry , latency of onset of cry , and Modified Facial Coding Score .  Thirty babies were enrolled in each of three groups . The groups did not differ significantly in baseline characteristics . Median ( interquartile range ) of duration of cry was least [ 34.6 ( 24.1–72.2 ) s ] in babies receiving EMLA cream with breastfeeding ( EB group ) , followed by 94.2 ( 46.1–180 ) s in babies receiving EMLA cream with oral distilled water ( EW group ) , as compared to 180.0 ( 180–180 ) s in babies receiving placebo cream with oral distilled water ( PCW group ) ( p < 0.05 ) . Mean ( SD ) of latency of cry was significantly greater in EB group [ 2.4 ( 1.14 ) s ] and EW group [ 1.9 ( 0.62 ) s ] as compared to babies in PCW group [ 1.5 ( 0.47 ) s ] ( p < 0.05 ) , but the difference between EB and EW groups was not significant . Modified Facial Coding Score was significantly lower in EB group as compared to the other groups ( p < 0.05 ) . Conclusions : Topical EMLA is effective in reducing pain and has a synergistic effect in analgesia when combined with breastfeeding during vaccination in infants The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Objective . To demonstrate that parent  application of eutectic mixture of local anesthetics ( EMLA ) results in equal reduction of the pain of intravenous ( IV ) placement compared with clinician application of EMLA , and to assess potential difficulties with parental application . Study Design . A 2 × 2 r and omized block design was used , with 41 children divided into two age groups ( 5–12 years vs 13–18 years ) and r and omized to one of two experimental groups ( parent-applied EMLA vs clinician-applied EMLA ) . Methods . All children were scheduled to have outpatient gastrointestinal endoscopies with IV sedation .  EMLA was placed at least 60 minutes before IV insertion either by the parent or a clinician , depending on the experimental group assignment . Outcome measures were child pain ratings and observed behavioral distress ratings .  Parents and children were interviewed to determine parent and child anxiety levels in anticipation of the IV insertion , previous needle stick experience , and previous difficulty coping . Feasibility outcomes included technical difficulty with application of EMLA and appearance of the EMLA cream and occlusive covering . Results . Pain ratings and behavioral distress ratings were generally in the low to moderate range for all groups and were consistent with previous empiric reports of EMLA outcome . There were no significant differences in pain or distress ratings for either the age or the experimental groups . Parent ratings of their child 's previous difficulty coping was related to the level of behavioral distress exhibited before ( r = .50 ) , during ( r = .32 ) and after ( r = .44 ) the IV insertion . In addition , children 's anxiety ratings about IV insertion seemed to differ among groups ( although not statistically significant for post hoc comparisons ) , with the most anxiety reported by the younger children when clinicians applied the EMLA and by older children when parents applied the EMLA . Conclusion . Parent application of EMLA appears to be as effective as clinician application in reducing children 's pain and distress associated with IV insertion . Permitting parents to apply the EMLA at home can allow children who are having procedures on an outpatient basis to benefit from topical anesthesia without having to arrive early to the clinic or hospital . Additionally , application by parents may result in less anticipatory anxiety for younger children BACKGROUND Untreated immunization pain causes undue distress and contributes to underimmunization through physician , and possibly parental , resistance to multiple simultaneous injections . OBJECTIVE To compare the efficacies of two pain management methods in reducing immediate immunization injection pain and distress in school-aged children . DESIGN A r and omized , controlled clinical trial of eutectic mixture of local anesthetics ( EMLA ) cream and vapocoolant spray . PATIENTS Children aged 4 to 6 years and scheduled to receive diphtheria and tetanus toxoids and acellular pertussis vaccine ( DTaP ) during health supervision visits . INTERVENTIONS Enrolled children were r and omized to one of three treatment groups : 1 ) EMLA cream + distraction ; 2 ) vapocoolant spray + distraction ; or 3 ) distraction alone ( control ) . The specific pharmacologic pain control interventions consisted of EMLA cream ( 2.5 % lidocaine , 2.5 % prilocaine [ Astra Pharmaceutical Products , Inc , Westborough , MA ] $ 15 . 00/patient ; applied 60 minutes before injection ) and vapocoolant spray ( Fluori-Methane [ Gebauer Company , Clevel and , OH ] $ 0 . 50/patient ; applied via spray-saturated cotton ball for 15 seconds immediately before injection ) . MAIN OUTCOME MEASURES The blinded investigator ( BI ) measured ( by edited videotape ) cry duration and the number of pain behaviors using the Observational Scale of Behavioral Distress . Pain visual analog scales ( linear and faces scales ) were completed by the child , parent , nurse , and the BI . RESULTS Sixty-two children , aged 4.5 + /- 0.4 years ( mean + /- SD ) were r and omized . The three treatment groups had similar subject characteristics . All pain measures and cry duration were similar for EMLA and vapocoolant spray . Both EMLA and spray were significantly better than control . Results for spray vs control : cry duration ( seconds ) : 8.5 + /- 21.0 vs 38.6 + /- 50.5 ; number of pain behaviors : 1.2 + /- 1.9 vs. 3.1 + /- 2.1 ; child-scored faces scale : 2.0 + /- 2.4 vs. 4.1 + /- 2.3 ; parent-scored faces scale : 1.6 + /- 1.6 vs. 3.0 + /- 1.7 ; nurse-scored faces scale : 1.6 + /- 1.2 vs. 3.1 + /- 1.4 ; and BI-scored faces scale : 1.0 + /- 1.5 vs. 2.4 + /- 1.4 . CONCLUSIONS When combined with distraction , vapocoolant spray significantly reduces immediate injection pain compared with distraction alone , and is equally effective as , less expensive , and faster-acting than EMLA cream . As an effective , inexpensive , and convenient pain control method , vapocoolant spray may help overcome physician and parent resistance to multiple injections that leads to missed opportunities to immunize PURPOSE To determine whether use of lidocaine-prilocaine 5 % cream ( EMLA ) decreases pain associated with diphtheria-pertussis-tetanus ( DPT ) vaccination in infants . METHODS R and omize , double-blind , controlled trial in outpatient pediatric practice , Toronto , Ontario , Canada . Before vaccination , parents applied 2.5 gm of EMLA or placebo to the infant 's leg and covered it with an occlusive dressing for at least 60 minutes . The infant received a 0.5 ml intramuscular injection of DPT at 2 degree to 8 degree C with a 1.6 cm 25-gauge needle ; the infant was videotaped . The Modified Behavioral Pain Scale ( MBPS ) was used to assess baseline and postvaccination pain scores . Latency and duration of infant cry were also measured . RESULTS A total of 49 evaluable infants received  EMLA , and 47 infants received  placebo . There were no significant differences in demographic data ; mean age was 5 months ; and 50 % of the subjects were male . The median difference in pre-vaccination and postvaccination MBPS scores was lower for EMLA than for placebo ( p = 0.001 ) . The latency to the first cry was longer for subjects who were treated with EMLA ( p = 0.0004 ) ) , but the total crying time was shorter ( 10.3 seconds vs 25.2 seconds ; p = 0.027 ) . Of the study group , 90 % ( 45/50 ) of subjects treated with EMLA and 12 % ( 6/49 ) of subjects treated with placebo had local skin reactions ( p < 0.0001 ) , mainly skin blanching . CONCLUSIONS Pretreatment with EMLA decreases infant pain from DPT vaccinations . Application of these data is limited to healthy infants receiving DPT vaccinations BACKGROUND AND OBJECTIVES Previous r and omized trials of the analgesic effects of sucrose , glucose , and a pacifier in term neonates have shown that the pacifier result ed in lower pain scores than glucose or sucrose , but the pacifier with and without sucrose did not differ . The current study was design ed 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 . PATIENTS AND METHODS In this double-blind , r and omized , controlled study , 36 preterm infants ( mean 31 weeks gestational age , range 27 to 36 weeks ) were r and omly 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 vali date d behavioral acute pain scale . RESULTS 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 ) . CONCLUSION The synergistic effect of the combination of sucrose and non-nutritive sucking was clinical ly 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 OBJECTIVE . The purpose of this work was to evaluate the analgesic properties of oral sucrose during routine immunizations in infants at 2 and 4 months of age . PATIENTS AND METHODS . A prospect i ve , r and omized , placebo-controlled clinical trial was conducted at a pediatric ambulatory care clinic . One-hundred healthy term infants scheduled to receive routine immunizations were recruited , r and omly stratified into 2- or 4-month study groups , and further r and omly assigned to receive 24 % oral sucrose and pacifier or the sterile water control solution . The study preparations were administered 2 minutes before the combined diphtheria-tetanus-acellular pertussis , inactivated polio vaccine , and hepatitis B vaccine . Haemophilus influenzae type b vaccine was administered 3 minutes after the combined injection , followed by the pneumococcal conjugate vaccine , 2 minutes after the H influenzae type b injection . The University of Wisconsin Children 's Hospital Pain Scale measured serial acute pain responses for the treatment and control groups at baseline and 2 , 5 , 7 , and 9 minutes after solution administration . Repeated- measures analysis of variance examined between-group differences and within-subject variability of treatment effect on overall pain scores . RESULTS . Two- and 4-month-old infants receiving oral sucrose ( n = 38 ) displayed reductions in pain scores 2 minutes after solution administration compared with 2- and 4-month-old infants in the placebo group ( n = 45 ) . Between-group comparisons for the oral sucrose and placebo groups showed lower pain responses at 5 , 7 , and 9 minutes after solution administration . The oral sucrose and placebo groups demonstrated their highest mean pain score at 7 minutes , with a mean pain score of 3.8 and 4.8 , respectively . At 9 minutes , the placebo group had a mean pain score of 2.91 whereas the mean pain score for the oral sucrose group returned to near baseline , reflecting a 78.5 % difference in mean pain score ( oral sucrose − placebo ) relative to the placebo mean . CONCLUSIONS . Oral sucrose is an effective , easy-to-administer , short-acting analgesic for use during routine immunizations CONTEXT Newborns are subject to pain during routine invasive procedures . Pain caused by immunization injections is preventable , but remains untreated in neonates . OBJECTIVES The purpose of the study was to compare the effectiveness of three nonpharmacological pain relief strategies on  newborns ' pain , physiological parameters , and cry duration before , during , and after hepatitis B  intramuscular ( IM ) injection . METHODS In this prospect i ve , r and omized clinical trial , we enrolled 165 newborns ( gestational age , ≥36 weeks ) . The infants received IM injections and were r and omized to three treatment groups : nonnutritive sucking ( NNS ) , 20 % oral sucrose , or routine care . Pain was measured by the Neonatal Facial Coding System , physiological signals by electrocardiogram monitors , and cry duration using a stopwatch . RESULTS Pain was significantly lower among infants in the NNS ( B=-11.27 , P<0.001 ) and sucrose ( B=-11.75 , P<0.001 ) groups than that in controls after adjusting for time effects , infant sleep/wake state , number of prior painful experiences , and baseline pain scores . Infants in the NNS and sucrose groups also had significantly lower mean heart and respiratory rates than the controls . Cry duration of infants receiving sucrose was significantly shorter than those in the NNS ( Z=-3.36 , P<0.001 ) and control groups ( Z=-7.80 , P<0.001 ) . CONCLUSION NNS and oral sucrose can provide analgesic effects and need to be given before painful procedures as brief as a one-minute IM injection . Sucrose orally administered two minutes before injection more effectively reduced newborns ' pain during injection than NNS . Both nonpharmacological methods more effectively relieved newborns ' pain , stabilized physiological parameters , and shortened cry duration  during IM hepatitis injection than routine care BACKGROUND Topical lidocaine 2.5 % and prilocaine 2.5 % ( EMLA ) is effective in decreasing the pain associated with minor procedures including immunization , although the effect on the antibody response to vaccine constituents has not been assessed . OBJECTIVE To measure the antibody response to measles-mumps-rubella ( MMR ) vaccine , as well as pain reduction associated with the use of the EMLA patch . PARTICIPANTS AND SETTING One hundred sixty healthy infants at least 12 months old undergoing their first MM immunization in an ambulatory setting . DESIGN AND INTERVENTIONS R and omized , double-blind , controlled trial of EMLA patch ( 5%-1 g ) or placebo before MMR immunization . Blood sampling before and 28 to 35 days after immunization . OUTCOME MEASURES The primary outcome measure was the antibody response to measles by plaque reduction neutralization and to mumps and rubella by enzyme immunoassay . The secondary outcomes were pain scores by the Modified Behavioral Pain Scale and drug- and vaccine-associated adverse events . RESULTS There was no difference in the antibody response between the EMLA- and placebo-treated groups . The response rates in the EMLA group were 89.7 % , 88.3 % , and 92.3 % to measles , mumps , and rubella , respectively , compared with rates of 91.1 % , 94.9 % , and 93.7 % in the placebo group ( P > .05 for all comparisons ) . EMLA recipients had less pain after immunization ( mean Modified Behavioral Pain Scale score increase 3.1 compared with 3.8 ; P = .043 ) and less irritability ( 16 % compared with 31 % ; P = .040 ) than did placebo recipients . CONCLUSIONS The EMLA patch has no adverse effect on the antibody response to MMR vaccine and significantly reduces the pain associated with the subcutaneous administration of the vaccine We investigated the effect of EMLA cream ( active ingredients : 25 mg lidocaine and 25 mg prilocaine per gram of cream ) on subjective experience of pain in connection with vaccination . The study was conducted as a double-blind , r and omized , placebocontrolled trial in a general practice setting . The subjects were ten to fifteen year-olds , who were due to be inoculated with measles-mumps-rubella vaccine .  Of the 118 children entering the trial , 117 completed the treatment ( EMLA 58 , placebo 59 ) . Treatment time was at least 60 minutes for all children . The children reported similar degrees of pain immediately after vaccination in both groups , one third of both treatment and placebo groups reporting medium to strong pain ( not significant ) . On the day after vaccination , more than half the families ( 59 % ) said that they would use the cream again in connection with future vaccinations ; again , there was no statistically significant difference between the two groups in this respect . Based on these results , we conclude that use of EMLA cream as a topical local anaesthetic does not reduce the experience of pain in connection with the administration of measles-mumps-rubella vaccine to older children Objectives To evaluate the effectiveness of topical eutectic mixture of local anaesthetics ( EMLA ® ) cream in reducing the pain associated with vaccination injections . Methods This was a r and omized , double-blind , placebo-controlled study that included children who presented for routine immunization . Eligible children were r and omly assigned to receive either EMLA ® or placebo cream . The Modified Behavioural Pain Scale ( MBPS ) was used to assess baseline and postvaccination pain scores , while a visual analogue scale ( VAS ) was used to assess pain at the time of the needle prick and at the end of the injection . Results A total of 107 children were enrolled in the EMLA ® group and 109 children in the placebo group . The difference between the pre- and postvaccination MBPS scores was significantly lower in the EMLA group than in the placebo group ( 2.56 ± 1.96 versus 3.95 ± 2.20 , respectively ) . The VAS scores at the time of the needle prick and after the injection were significantly lower in the EMLA ® group compared with the placebo group ( 1.60 ± 1.67 versus 3.24 ± 2.01 ; 3.29 ± 2.27 versus 4.86 ± 2.20 ; respectively ) . Conclusions Application of EMLA ® cream can be effectively incorporated as a routine pain-relieving intervention within routine vaccination appointments The objective was to examine the antibody responses to influenza immunization in an elderly population and the effect of prophylactic acetaminophen on adverse responses due to inactivated whole virus vaccine containing influenza A ( H3N2 and H1N1 ) and B antigens . During the autumn of 1990 , 100 patients 65 years or older were immunized and r and omly allocated to receive placebo or 1,950 mg ( 2 x 975 mg ) of acetaminophen . They recorded any local and systemic side effects over a 3-day period . Serology was performed on pre- and post ( 4 - 6 weeks ) -vaccination sera . Age and gender distribution in the study were : 47 % who were 75 years or older , and 61 % of the patients were female . Most of the patients ( 97 % ) had pre-existing antibodies to Influenza A or B.  Average peak preimmunization antibody titers were 40 to B Yamagata and A Taiwan ( H1N1 ) and 80 for A Shanghai ( H3N2 ) . Half of each treatment group had a 4-fold or greater rise in antibody titer in response to the vaccine . Only 30 % of patients immunized the previous year but 80 % of those never vaccinated previously demonstrated a 4-fold or greater serological response to the vaccine . However , measurement of protection rates ( HI > /= 40 ) before and after vaccination indicated 81.1 - 100 % protection for the 3 viruses not influenced by treatment , gender or a history of previous vaccination . Both treatment groups had equally small numbers of patients who recorded systemic symptoms of drowsiness , myalgia , fever and chills and about 50 % had arm soreness . Although about 80 % of previously unimmunized adults mounted a 4-fold antibody rise to influenza vaccine antigens whereas booster effects were seen in only 30 % of those immunized the previous year , protection rates were high ( 81 - 100 % ) after immunization and were not affected by acetaminophen treatment . Adverse effects ( 15 % systemic and 50 % local ) were not ameliorated by 1950 mg of acetaminophen in these elderly patients The analgesic effects of four solutions administered intra-orally ( 25 and 50 % sucrose solutions , hydrogenated glucose , and a sterile water placebo ) were tested in groups of babies receiving routine DTP ( diphtheria , tetanus , and pertussis ) and HIB ( Haemophilus influenzae type B ) injections at the first , second , or third immunization . The duration of the baby ’s cry during 3 min following DTP and HIB injections was measured as main outcome . For all three immunization groups , the babies receiving the placebo generally spent most time crying . For both the DTP and HIB injections , the difference between 50 % sucrose and placebo was most evident in the group receiving the 3rd immunization . Intra-oral administration of the 50 % sucrose solution , compared to placebo , appeared to reduce the cry response to painful experiences in babies beyond the neonatal period OBJECTIVE To assess the effectiveness of sucrose as an analgesic agent during routine immunization injections for infants ( age range , 2 weeks to 18 months ) . STUDY DESIGN Double-blind , r and omized control trial . SETTING Ambulatory care clinic of a large tertiary care center . PARTICIPANTS A consecutive sample of 285 infants were r and omly assigned to one of three treatment groups . INTERVENTION 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 . MAIN OUTCOME MEASURE Infants were videotaped during immunization for later interval recording of pain-induced vocalizations . RESULTS 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 ) . CONCLUSIONS 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 exp and 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 PURPOSE To evaluate the effectiveness and age-related changes in analgesia of oral sucrose as a preprocedural intervention during routine immunizations in infants at 2 and 4 months of age . DESIGN A double-blind , r and omized , placebo-controlled clinical trial of 40 healthy term infants scheduled to receive routine immunizations from a pediatric ambulatory care clinic during May 2005 to July 2005 . METHODS Infants received 24 % oral sucrose solution or the control solution of sterile water 2 minutes before routine immunizations at both their 2- and 4-month , well-child visits . The University of Wisconsin Children 's Hospital pain scale was used to measure serial acute behavioral pain responses at baseline , 2 , and 5 minutes after administration of the solution . Repeated measures ANOVA was used to examine between-group differences and within-subject variability of the effects of treatment on overall behavioral pain scores . FINDINGS Infants receiving oral sucrose ( n=20 ) showed a significant reduction in behavioral pain response 5 minutes after administration compared to those in the placebo group ( n=20 ) . At 2 minutes following solution administration , both sucrose and sterile water showed the highest mean pain score ( 4.54 and 4.39 respectively ) indicating a severe amount of pain . At 5 minutes , the sucrose group returned to near normal at 0.27 while the placebo group remained at 3.02 indicating a percentage difference in mean pain scores relative to sterile water pain scores of 90.9 . No statistically significant age-related change in behavioral pain response was noted between 2- and 4-month-old infants at 2 minutes and 5 minutes following treatment administration . CONCLUSION Sucrose is an effective preprocedural intervention for decreasing behavioral pain response in infants after immunizations . CLINICAL RELEVANCE Efforts to decrease the pain associated with immunizations can promote parental adherence to recommended immunizations schedules , prevent a resurgence of vaccine-preventable diseases and mitigate adverse neurologic outcomes in infants The effectiveness of a eutectic mixture lidocaine‐prilocaine topical anaesthetic cream ( EMLA ® ) patch compared with a placebo patch in the reduction of pain associated with intramuscular immunization was evaluated . As part of the study , 161 children ( aged 4‐6‐y ) undergoing routine diphtheria , pertussis , tetanus and polio ( DPTP ) immunization in five urban and five rural private office setting s were r and omly assigned to an EMLA ® patch ( n= 83 ) or a placebo patch control group ( n= 78 ) . Pain measurements included : child 's self‐report on a Faces Pain Scale ; facial action on the Child Facial Coding System ; the Children 's Hospital of Eastern Ontario Pain Scale and parent and technician ratings on a Visual Analogue Scale . Parents also rated their own and their child 's immunization‐related anxiety on a Visual Analogue Scale . The EMLA ® patch group had significantly less pain on all four pain measures compared with the placebo group . Of the children in the placebo group , 43 % had clinical ly significant pain , compared with 17 % of children in the EMLA ® patch group . No severe adverse symptoms occurred as a result of either EMLA ® or placebo patch application BACKGROUND Although fever is part of the normal inflammatory process after immunisation , prophylactic antipyretic drugs are sometimes recommended to allay concerns of high fever and febrile convulsion . We assessed the effect of prophylactic administration of paracetamol at vaccination on  infant febrile reaction rates and vaccine responses . METHODS In two consecutive ( primary and booster ) r and omised , controlled , open-label vaccination studies , 459 healthy infants were enrolled from ten centres in the Czech Republic . Infants were r and omly assigned with a computer-generated r and omisation list to receive three prophylactic paracetamol doses every 6 - 8 h in the first 24 h ( n=226 ) or no prophylactic paracetamol ( n=233 ) after each vaccination with a ten-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine ( PHiD-CV ) co-administered with the hexavalent diphtheria-tetanus-3-component acellular pertussis-hepatitis B-inactivated poliovirus types 1 , 2 , and 3-H influenzae type b ( DTPa-HBV-IPV/Hib ) and oral human rotavirus vaccines . The primary objective in both studies was the reduction in febrile reactions of 38.0 degrees C or greater in the total vaccinated cohort . The second objective was assessment of immunogenicity in the according-to- protocol cohort . These studies are registered with Clinical Trials.gov , numbers NCT00370318 and NCT00496015 . FINDINGS Fever greater than 39.5 degrees C was uncommon in both groups ( after primary : one of 226 participants [ < 1 % ] in prophylactic paracetamol group vs three of 233 [ 1 % ] in no prophylactic paracetamol group ; after booster : three of 178 [ 2 % ] vs two of 172 [ 1 % ] ) . The percentage of children with temperature of 38 degrees C or greater after at least one dose was significantly lower in the prophylactic paracetamol group ( 94/226 [ 42 % ] after primary vaccination and 64/178 [ 36 % ] after booster vaccination ) than in the no prophylactic paracetamol group ( 154/233 [ 66 % ] after primary vaccination and 100/172 [ 58 % ] after booster vaccination ) . Antibody geometric mean concentrations ( GMCs ) were significantly lower in the prophylactic paracetamol group than in the no prophylactic paracetamol group after primary vaccination for all ten pneumococcal vaccine serotypes , protein D , antipolyribosyl-ribitol phosphate , antidiphtheria , antitetanus , and antipertactin . After boosting , lower antibody GMCs persisted in the prophylactic paracetamol group for antitetanus , protein D , and all pneumococcal serotypes apart from 19F . INTERPRETATION Although febrile reactions significantly decreased , prophylactic administration of antipyretic drugs at the time of vaccination should not be routinely recommended since antibody responses to several vaccine antigens were reduced . FUNDING GlaxoSmithKline Biologicals ( Belgium ) OBJECTIVE To assess the effect of Eutectic Mixture of Local Anaesthetics cream and rattle on soothing the vaccination pain on four-month-infants . METHODS The single blind r and omised clinical trial was conducted from May 2012 to February 2013 at a clinic under the Gonabad University of Medical Sciences , Iran , and comprised four-month infants who were selected r and omly and divided into three groups . In one group , 2 g of eutectic mixture of local anaesthetics cream was rubbed on the injection spot before administration ; for the other group , the rattle was shaken from 30s to 15s before injection . The last group consisted of controls . The infants were filmed after vaccination . Afterward , a pain question naire was filled out by a trained observer . SPSS 11.5 was used for statistical analysis . RESULTS Of the 50 subjects in the study 16 ( 32 % ) each were in the cream and rattle groups , while the rest ( 36 % ) were in the control group . The severity of the pain before intervention in the control , cream and rattle groups was 2.22 + /- 0.88 , 2.12 + /- 0.95 and 2.25 + /- 1.06 respectively , which were not statistically significant ( p < 0.93 ) . Likewise , the mean severity of pain at the moment of intervention in the three above groups were 8.67 + /- 0.77 , 7.12 + /- 0.5 and 7.87 + /- 0.96 respectively , which was significantly different ( p < 0.001 ) . The severity of pain 15seconds after the intervention in the groups was 5.06 + /- 1.51 , 4.87 + /- 1.31 and 4.19 + /- 1.94 respectively , which were not statistically different ( p < 0.27 ) . CONCLUSION The eutectic mixture of local anaesthetics cream and shaking rattle were effective in attenuating pain of vaccination among the infants , but the latter was not as significant as the former Although immunization injections are the most common painful medical procedures , pain-relieving interventions are not routinely used . In this r and omized controlled trial , we compared the effectiveness of topical anesthesia using liposomal lidocaine to : ( 1 ) vapocoolant spray using a proprietary blend of 1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluoroethane ; ( 2 ) nurse-administered tactile stimulation ; or ( 3 ) self-directed distraction by means of reading a magazine . Liposomal lidocaine was more effective ( p < or=0.05 ) than distraction , as assessed by self-reported pain using the visual analog scale and global report , but did not differ from either vapocoolant spray or tactile stimulation . This information can be incorporated in immunization programs The need for developing a case definition and guidelines for a local reaction at or near the injection site , methods for the development of the case definition and guidelines as an adverse event following immunization as well as the rationale for selected decisions about the case definition for a local reaction at or near the injection site are explained in the Preamble section . The case definition is structured in 2 levels of diagnostic certainty : level 1 includes any description of morphological or physiological change at or near the injection site that is described or identified by a healthcare provider . Level 2 is any description of morphological or physiological change at or near injection site that is described by any other person . In Guidelines section , the working group recommends to enable meaningful and st and ardized data collection , analysis , and presentation of information about a local reaction at or near the injection site . However , implementation of all guidelines might not be possible in all setting s. The availability of information may vary depending upon re sources , geographic region , and whether the source of information is a prospect ively design ed clinical trial , a post-marketing surveillance or epidemiologic study , or an individual report of a local reaction at injection site BACKGROUND : Pain is a global health problem which exists from birth to the last stages of our life . It has been proven that infants are able to feel the painful stimulus . Infants routinely experience the pain in the hospitals especially during the vaccination procedure . Therefore , finding a non pharmacological pain relieving method is necessary . The aim of this study was to compare the pain relieving effect of oral sucrose , breastfeeding and combination of them during the first vaccination of infants with less than 3 months of age . METHODS : In this quasi-experimental study , 120 infants under 3 months of age who referred to Tabriz Health Centers in 2009 were categorized r and omly in four groups ;  25%oral sucrose , breastfeeding , combined method and control groups . In the case groups , vaccination was implemented two minutes after the mentioned intervention . Neonatal Infant Pain Scale ( NIPS ) was used to determine the pain score at 0 , 5 and 10 minutes after the vaccination . The duration of the infants ’ crying and pulse rate was also measured . The data were analyzed using the SPSS software and statistical chi-square , ANOVA and Kruskal-Wallis tests . RESULTS : The findings of the present study indicated that in breastfeeding group the mean pain score was the lowest immediately after the vaccination , but this difference was significant only in breastfeeding and control groups ( p = 0.007 ) . The minimum crying time was 66.6(32.62 ) seconds in breastfeeding group and the maximum time was 126.26(46.15 ) seconds in control group . The ANOVA test results showed that all the conducted interventions made a significant reduction of crying time in comparison with the control group . The ANOVA also showed that none of the above interventions had any effect on preventing from the increase of the following tachycardia . CONCLUSIONS : According to the findings of the present study , the lowest pain score and crying time was in breastfed neonates . Considering the fact that breastfeeding is a natural , useful and free intervention and does not need any special facility , this method is suggested in pain management and control during painful procedures for infants The analgesic effect of topical ibuprofen was investigated in ten volunteers . There were no significant differences in visual analogue scale pain scores for pinprick after 15 and 60 mm of application of ibuprofen , placebo and EM LA cream . Comparison of visual analogue scale scores for venous cannulation after similar duration s of ibuprofen and EMLA creams found significantly ( p < 0.014 ) lower scores for EMLA at 60min . We do not consider ibuprofen cream to be clinical ly useful for venous cannulation Objectives The purpose of this study was to evaluate the effectiveness of vapocoolant for preschoolers ' immunization injection pain relief  . Methods Fifty-seven 4 to 6-year-old children were  r and omized  into vapocoolant alone or typical care conditions .  Pain was measured at the baseline and at injection via self-report , caregiver report , nurse report , and by an observational scale . Results Self-report of pain suggested that children in the vapocoolant alone condition demonstrated stronger increases in pain from baseline to injection than children in the typical care condition . All other measures showed significant increases in pain from baseline to injection , but no other measures indicated treatment effects . Discussion This study revealed that vapocoolant is not an effective pain management intervention for children 's intramuscular injections Although the analgesic effect of sucrose on newborns is well established , little is known about whether these solutions are effective in reducing procedural pain in infants beyond the newborn period . The purpose of this study was to determine the effect of sucrose solution given orally on infant crying times and measure the distress in a 16–19-month age group . A total of 537 healthy , 16–19-month-old infants attending for their immunizations with intramuscular diphtheria , tetanus , and acellular pertussis (DTaP)/Haemophilus influenza type b/IPV ( along with oral polio vaccination ( OPV ) ) , intramuscular pneumococcus and intramuscular hepatitis A were r and omized to receive 2 mL of a 75 % sucrose solution , a 25 % sucrose solution or sterile water 2 min before injections . Infants receiving a 75 % sucrose solution had significantly reduced total crying times and Children ’s Hospital of Eastern Ontario Pain Scale scores ( CHEOPS ) compared with infants in the control and 25 % sucrose solution groups ( p < 0.001 ) . Conclusion : Sucrose solution reduces infant distress and is safe and clinical ly useful even for 16–19-month-old infants OBJECTIVE : The goal was to compare the efficacy of oral 25 % dextrose treatment and /or skin-to-skin contact for analgesia in term newborns during intramuscular injection of a hepatitis B vaccine . METHODS : A prospect i ve , r and omized , partially blinded , clinical trial was performed with 640 healthy term newborns . Infants at 12 to 72 hours of life were assigned r and omly to receive an intramuscular injection of hepatitis B vaccine in the right thigh according to 4 analgesia groups , that is , no analgesia ( routine ) ; oral 25 % dextrose treatment , given 2 minutes before the injection ; skin-to-skin contact , initiated 2 minutes before the injection and persisting throughout the procedure ; and a combination of the oral dextrose treatment and skin-to-skin contact strategies . For all groups , Neonatal Facial Coding System and Neonatal Infant Pain Scale scores were evaluated before the procedure , during thigh cleansing , during the injection , and 2 minutes after the injection . Premature Infant Pain Profile scores also were assessed for all infants . Pain scores were compared among the 4 groups . RESULTS : The use of oral 25 % dextrose treatment reduced the duration of procedural pain in the studied population . Skin-to-skin contact decreased injection pain and duration . The combination of the 2 analgesic measures was more effective than either measure separately for term newborns . CONCLUSIONS : Nonpharmacologic analgesic measures were effective for the treatment of procedural pain in term infants . The combination of oral 25 % dextrose treatment and skin-to-skin contact acted synergistically to decrease acute pain in healthy neonates Although pain management is an important nursing responsibility , few interventions for minimizing distress of infants during painful procedures have been studied . Sixty infants , 2 through 6 months of age , were studied during a routine DPT immunization in order to examine ( a ) the effectiveness of cooling the skin in reducing distress behaviors and ( b ) the relationship between age and distress behavior . Infants were r and omly assigned to experimental or control groups . Prior to the injection , the sites were sprayed for 2 to 3 s with either a skin refrigerant/anesthetic or compressed air . Behaviors were video- and audio-taped during and 60 s post injection , and coded for ( a ) facial expression , ( b ) cry , and ( c ) body movements . MANOVA revealed fewer distress behaviors following refrigerant spray and more complex , varied behavioral responses for older infants . The findings provide further evidence that infants perceive pain and that nursing interventions for pain reduction should be tested and extended to the very young BACKGROUND Comprehensive international travel preparation often requires several vaccines . Up to 90 % of adults have some fear of injections , mostly due to injection-related pain . Pediatric studies with routine vaccines have shown topical anesthetic EMLA cream ( lidocaine and prilocaine , Astra Pharmaceuticals , Inc. ) and the topical vapocoolant Fluori-Methane ( dichlorodifluoromethane and trichlorodifluoromethane , Gebauer Co. ) to be equally effective in reducing pain from vaccinations . EMLA cream is expensive and requires a 60-min application , while Fluori-Methane ( FM ) is immediate in onset of action and inexpensive . Skin anesthesia begins at 10 degrees C. Fluori-Methane can briefly cool the skin to 0 degrees C. METHODS We studied the effectiveness of topical vapocoolant on adult clients at our international travel clinic in a r and omized , controlled trial of topical FM vs. cold ( 4 degrees C ) saline placebo . Using a preset r and omization table , participants served as their own controls , receiving placebo/control or active agent ( participant blinded ) in one arm ( left or right ) , and a similar number of vaccines in the untreated arm . Vaccines were administered according to a set protocol per arm to minimize the risk of bias . Pain was measured using a modified McGill present pain intensity ( PPI ) pain index . Subjects rated their pain immediately and at 5 min on a six-level scale , noting treated and untreated arms separately . A question naire was completed on intervention preferences . Sample size was predetermined to achieve 90 % statistical power estimating 25 % efficacy ( minimum n=172 ) . RESULTS One hundred and eighty-five participants were enrolled ; 93 FM and 92 cold saline placebo .  FM-treated arms had a significant reduction in immediate pain compared to untreated arms ( pain scale mean 2.2 vs. 3.1 ; p<.0001 ) , and compared to placebo ( mean 2.2 vs. 2.8 ; p<.01 ) . Delayed pain at 5 min was not affected by FM or control ( mean 1.9 vs. 2.0 ) compared to no intervention ( pain scale 1.9 ) . The intervention preference question naire indicated that participants did not find FM therapy uncomfortable . They would choose FM therapy in the future , over a cream , especially if a wait was involved . CONCLUSION The topical vapocoolant Fluori-Methane is an effective , quick , preferred , inexpensive agent for reducing vaccine-associated injection pain for international travel clients & NA ; The objective of this study is to determine whether use of lidocaine – prilocaine 5 % cream ( EMLA ® ) and oral glucose decreases pain associated with diphteria – pertussis – tetanus ( DPT ) immunization in 3‐month‐old infants . Design : r and omized , double‐blind , controlled trial in outpatient paediatric practice in northern Sweden .  EMLA or placebo was applied to the infant 's lateral region of the right thigh and covered with an occlusive dressing 1 h before the immunization . In addition , 1 ml of glucose ( 300 mg/ml ) or placebo ( water ) was instilled on the baby 's tongue within 2 min before the DPT‐injection . Forty‐five infants received EMLA and glucose  and 45 infants placebo cream and water . ECG was recorded and stored in a computer and the procedure was videotaped . The parents and the nurse assessed the infants ' pain on a visual analogue scale ( VAS ) after the immunization . Heart rate and heart rate variability pre‐ and post‐injection were calculated . From the videotapes , the modified behavioural pain scale ( MBPS ) was used to assess pain scores during baseline and after immunization . The latency of the first cry and total crying time were measured . The parents and the nurse scored the infants ' pain on the VAS significantly lower in the treatment group than in the placebo group . The infants ' responses to the immunization measured as the difference in MBPS scores pre‐ and post‐injection were significantly lower in the EMLA – glucose group compared with the placebo group . More infants cried after the immunization in the placebo group compared with the EMLA – glucose group and the latency of the first cry after the injection was shorter in the placebo group . A biphasic transient heart rate response with a marked deceleration followed by a subsequent acceleration was seen more frequently in the placebo group compared to the EMLA – glucose group . EMLA and glucose  alleviate immunization pain in 3‐month‐old infants In human newborns , small amounts of sucrose reduce crying with procedural pain by about 50 % . To determine whether “ sucrose analgesia ” could be extended to painful procedures beyond the newborn period , 57 infants were r and omly assigned to receive three 250-$mUl doses of 50 % sucrose solution ( g/100 mL ) or water before their diphtheria-tetanus-pertussis immunizations at 2 and 4 months of age . Crying during and after injection was measured separately to determine whether sucrose modified crying during the noxious stimulus , recovery from the stimulus , or both . Sucrose was effective in reducing crying only from 83 to 69 % , and the reduction was limited to the postinjection period . We conclude that , although sucrose continues to have some effect beyond the newborn period , the effect is limited to recovery from the noxious stimulus , is clinical ly modest , and is probably smaller than in the newborn period Eighteen , healthy male newborns , 2–5 days old , were subjects in this study of the effects of a pacifier on the newborn 's behavioral and adrenocortical responses to circumcision . Half of the subjects were r and omly assigned to a condition in which they were encouraged to suck on a pacifier during circumcision , while half served in a no pacifier , control condition .  Behavioral observations were made for 1/2 hour before , during , and after circumcision ; while blood sample s for serum cortisol determination were obtained immediately before circumcision and 30 min later . The results showed that stimulating the newborn with the pacifier  reduced crying by about 40 % . Reducing crying , however , had no significant effect on the adrenocortical response . Elevations of serum cortisol predicted average behavioral state following circumcision , whereas crying during circumcision did not . Furthermore , there was evidence that the neonatal adrenocortical system was sensitive to variations in surgical procedures . The results indicate the importance of obtaining data on both behavioral and hormonal systems in studies of stress and coping in human newborns BACKGROUND Infant immunisation is the most commonly performed health procedure in developed countries . Associated pain may be harmful because we do not know what painful experiences the infant has already had and whether it might contribute to a cumulative pain experience . Healthy infants undergo immunisation with minimal pain relief . However , immunisation pain can be managed using oral sweet solutions . OBJECTIVE To determine the effectiveness of 25 % oral glucose solution in reducing immunisation pain in 2-month old infants . TRIAL DESIGN AND METHODS : A double-blind , r and omised controlled trial conducted in Jordan . A total of 120 healthy full-term infants who met the eligibility criteria and were attending immunisation clinics for routine 2-month immunisation were r and omised to receive either 2 mL of 25 % oral glucose solution immediately prior to their immunisation or 2 mL of oral sterile water . Research ers , nurses and parents were blind to the solution . Primary outcome was behavioural pain measured using the Modified Behavioural Pain Scale ( MBPS ) . Secondary outcomes were crying time and duration of full-lung cry . Crying was registered from onset of the immunisation injection and for up to 120 s after completion of the injection procedure . RESULTS Infants in the intervention group experienced statistically and clinical ly significant reduction in behavioural pain responses ( p<0.001 ) , and spent less time crying up to 2 min after the procedure ( mean difference 38 vs. 77.9s ) . CONCLUSION A 2 mL oral dose of 25 % glucose given immediately before an immunisation procedure reduces pain in 2-month old infants
BACKGROUND This systematic review assessed the effectiveness and safety of pharmacotherapy and combined interventions for reducing vaccine injection pain in individuals across the lifespan .