A randomized trial of the effect of vaccine injection speed on acute pain in infants.

OBJECTIVE: This study compared the pain caused from fast vs. slow vaccine injections. METHODS: Infants aged 2-6months receiving primary immunizations were randomized to fast (2-4mL/s) or slow (5-10mL/s) injections during routine 0.5mL Diphtheria, Tetanus, acellular Pertussis, Inactivated Polio Virus, Haemophilus influenzae type b vaccine (DTaP-IPV-Hib) injections. Those aged 2 and 4months additionally received 0.5mL Pneumococcal Conjugate Vaccine (PCV) injections. A research assistant and parent unaware of treatment allocation and hypothesis assessed pain using validated and recommended tools, including; the Modified Behavioural Pain Scale (MBPS, range 0-10), cry duration, and Numerical Rating Scale (NRS, range 0-10). The primary outcome was infant pain score using the MBPS. RESULTS: Altogether, 120 were recruited; 61 were randomized to fast injections and 59 to slow injections. One hundred and ninteen infants participated. There were no differences in characteristics, including; age (p=0.994) and sex (p=0.540). The mean MPBS score (standard deviation) during DTaP-IPV-Hib injection was lower in the fast injection group: 6.4 (2.7) vs. 7.4 (2.5), respectively; p=0.046. Regression analysis demonstrated a positive correlation between injection speed and pain. There were no other differences between groups. CONCLUSION: Fast injection reduced injection-induced pain in infants receiving DTaP-IPV-Hib but not PCV vaccine. Fast injections are recommended when administering vaccines because of the potential for a reduction in pain, feasibility and practicality. TRIAL REGISTRATION: NCT02504398.

Reliability and validity of observer ratings of pain using the visual analog scale (VAS) in infants undergoing immunization injections.

We tested the reliability and validity of observer-rated pain in infants undergoing immunization using the visual analog scale (VAS). Pain was assessed in real time and later, from videotapes, in 120 1-year-old infants participating in a double-blind randomized controlled trial of amethocaine vs. placebo. Altogether, 2 (1 physician, 1 non-physician) of 4 raters [2 physicians, 2 non-physicians (nurse and graduate student)] independently assessed baseline and vaccine injection pain using a 100mm unmarked VAS line. Intra- and inter-rater reliability, assessed using the intra-class correlation coefficient (ICC), ranged from 0.69 to 0.91 and 0.55 to 0.97, respectively. Bland-Altman plots demonstrated no evidence of bias between real time and video assessments. When scores were dichotomized into 2 groups (no pain and pain) using a cut-off of >or=30mm, intra-rater reliability ranged from 0.35 to 0.92. The percent of scores deviating by >20mm was 4.5-14.29%. Criterion validity was demonstrated by correlations between the VAS and Modified Behavioural Pain Scale, a validated observational measure; (rho: 0.81-0.94). Injection scores were lower in the amethocaine group, when comparing difference (baseline-injection) or dichotomized scores; significance (p<0.036) was achieved for non-physician scores, but not physician scores. Together, these results provide initial support for the VAS as an outcome measure for acute procedural pain in infants. However, different conclusions may be reached about the effectiveness of analgesic interventions depending on the rater. Sources of variability include use of multiple raters, rater focus (procedure vs. child) and experience level.

Order of vaccine injection and infant pain response.

OBJECTIVE: To determine if acute pain response after administration of the diphtheria, polio, and tetanus toxoids and acellular pertussis and Haemophilus influenzae type b (DPTaP-Hib) vaccine and the pneumococcal conjugate vaccine (PCV) is affected by the order in which they are given. DESIGN: Single-center, double-blind, randomized clinical trial. SETTING: Outpatient pediatric clinic in Toronto, Ontario, Canada. PARTICIPANTS: Healthy infants 2 to 6 months of age undergoing routine immunization. INTERVENTIONS: Infants received either their primary DPTaP-Hib vaccine or the PCV first, followed by the other vaccine. MAIN OUTCOME MEASURES: The primary outcome was infant pain during vaccine injection as assessed by a validated measure, the Modified Behavioral Pain Scale (MBPS), using videotaped recordings of the procedure. In addition, parents rated pain using a 10-cm visual analog scale (VAS). Crying (yes/no) was also measured. RESULTS: The study was conducted between July 21, 2006, and June 21, 2007. A total of 120 infants participated: 60 received the DPTaP-Hib vaccine first and 60 received the PCV first. Infant characteristics did not differ between groups. Overall mean (SD) pain scores per infant after receiving both vaccine injections were significantly lower when DPTaP-Hib was administered first compared with when PCV was administered first (MBPS score, 7.6 [1.5] vs 8.2 [1.5], P = .037; parent VAS score, 4.2 [2.3] vs 5.6 [2.6], P = .003). When given first, the DPTaP-Hib vaccine caused significantly less pain (P < .001) than the PCV, as assessed by the MBPS, VAS, and crying. CONCLUSIONS: Pain was reduced when the DPTaP-Hib vaccine was administered before the PCV in infants undergoing routine vaccination. We recommend that the order of vaccine injections be the DPTaP-Hib vaccine followed by the PCV.

Pain response to M-M-R vaccination in 4-6 year old children.

BACKGROUND: Differences in pain response to two different M-M-R products have previously been demonstrated in 12-month old infants and in 4 â 6 year old children. Objective To determine if the acute and immediate pain response to two licensed M-M-R vaccine products (using a self-report measure) in children 4-6 years of age was similar to that demonstrated in younger infants. METHODS: Randomized, double blind, study. Subjects were randomly allocated to PriorixA (SmithKline Beecham) or M-M-R IIA (Merck Frosst). The primary outcome measure was pain response to vaccination quantified using a self-report OUCHER pain scale. Secondary outcome measures included pain measurement by proxy (physician and parent) using a visual analog scale (VAS) and measurement of cry and cry duration immediately post-vaccination. RESULTS: Of the 60 subjects enrolled, 30 received PriorixA and 30 received M-M-R IIA. There were no significant differences between the two groups on age, sex, or previous painful procedure. Post-vaccination, children in the M-M-R IIA group had higher median pain scores compared with children in the PriorixA group for VAS (12.5 vs. 2.0, respectively by paediatricians, p=0.017; 18.5 vs. 5.0, respectively by parents, p=0.235), OUCHER (20 vs. 0.00, respectively, p=0.047). The median duration of crying post M-M-R IIA was higher compared with PriorixA (6 vs. 0 seconds, respectively, p=0.020). Conclusion PriorixA was associated with significantly less pain compared with M-M-R IIA, at the time of injection.

Topical 4% amethocaine gel reduces the pain of subcutaneous measles-mumps-rubella vaccination.

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 settings. 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, randomized, 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 (standard 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.

Effects of age, gender and holding on pain response during infant immunization.

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

Effect of choice of measles-mumps-rubella vaccine on immediate vaccination pain in infants.

OBJECTIVE: To compare acute pain response to 2 measles-mumps-rubella vaccines. DESIGN: Double-blind clinical trial. SETTING: Hospital for Sick Children, Toronto, Ontario. Patients Forty-nine infants 12 months of age receiving their first measles-mumps-rubella vaccination. INTERVENTIONS: Random allocation to receive Priorix or M-M-R II. MAIN OUTCOME MEASURES: Pain responses before (baseline) and after (within 15 seconds) vaccination were quantified by visual analog scale (VAS; range, 0-100), completed by the parent and independently by the pediatrician, and the Modified Behavioral Pain Scale (range, 0-10), scored by a coder blinded to the vaccine allocation. Crying (yes or no) and latency to the first cry after injection were also measured. RESULTS: Twenty-six infants received Priorix and 23 received M-M-R II. There were no differences between the 2 groups in baseline characteristics or prevaccination baseline pain scores. Median pain scores after vaccination (Priorix vs M-M-R II) were as follows: pediatrician VAS, 15 vs 58 (P =.001); parent VAS, 22 vs 53 (P =.007); and Modified Behavioral Pain Scale, 6 vs 8 (P =.02). Median difference in pain scores (after minus before) for Priorix vs M-M-R II were as follows: pediatrician VAS, 15 vs 53 (P =.003); parent VAS, 22 vs 47 (P =.008); and Modified Behavioral Pain Scale, 3 vs 5 (P =.03). The median latency to first cry was 1.5 seconds in the Priorix group compared with 1 second in the M-M-R II group (P =.26). CONCLUSIONS: Priorix vaccine causes significantly less pain than M-M-R II at the time of injection for 12-month-old infants receiving their first measles-mumps-rubella vaccination.