A pain-relieving strategy
for childhood vaccination
Manal Abuelkheir1, Deema Alsourani2,
Ayman Al-Eyadhy3, Mohamad-Hani Temsah3,
Sultan Ayoub Meo4and Fahad Alzamil3
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 randomized, double-blind, placebo-controlled study that included children
who presented for routine immunization. Eligible children were randomly 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: Atotal of107 children wereenrolled 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
Conclusions: Application of EMLA?cream can be effectively incorporated as a routine pain-
relieving intervention within routine vaccination appointments.
Eutectic mixture of local anaesthetics (EMLA?), childhood vaccination, pain assessment,
Date received: 22 September 2013; accepted: 28 September 2013
Journal of International Medical Research
2014, Vol. 42(2) 329–336
! The Author(s) 2014
Reprints and permissions:
1Department of Clinical Pharmacy, King Khalid University
Hospital, King Saud University, Riyadh, Saudi Arabia
2Department of Paediatrics, King Khalid University
Hospital, King Saud University, Riyadh, Saudi Arabia
3Department of Paediatrics, College of Medicine, King
Saud University, Riyadh, Saudi Arabia
4Department of Physiology, College of Medicine, King Saud
University, Riyadh, Saudi Arabia
Dr Manal Abuelkheir, Pediatric Clinical Pharmacist,
Department of Pharmacy, King Khalid University Hospital,
PO Box 7805, Riyadh 11472, Saudi Arabia.
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distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page
Pain in children is underestimated globally
and continues to be suboptimally mana-
ged.1–3Currently, vaccine injections are
considered to be
source of iatrogenic pain in childhood.3,4
They are repeatedly administered to almost
all children throughout infancy, childhood
and adolescence. Vaccine injections cause
patients.5,6The pain associated with such
injections is not only a source of distress
for children, but also for their parents and
the individuals administering the injec-
tions.4This pain can lead to preprocedural
anxiety in the future, needle phobias and
healthcare avoidance behaviours.5
estimated that up to 25% of adults have
a fear of needles, with most fears develop-
ing in childhood.6Conversely, more posi-
tive experiences during vaccine injections
would promote and maintain trust in
Eutectic mixture of local anaesthetics
(EMLA?) cream is a topical anaesthetic
mixture of lidocaine (2.5%) and prilocaine
(2.5%) in a cream base.7Eutectic mixtures
are combinations of two or more substances
that solidify at a lower temperature than
their individual ingredients. Given its safety
profile and proven efficacy, the application
of EMLA?cream before vaccination of
children to reduce pain at the time of
injection is recommended by the Canadian
guidelines for reducing the pain of child-
hood vaccination (grade A recommenda-
tion, based on level I evidence).8However,
many paediatricians and healthcare pro-
viders report that one of the major barriers
against the routine implementation of such
pain-relieving interventions is insufficient
time to incorporate them within the busy
office workflow, because of the delayed
onset of the anaesthetic effect (60min).3,9
The aim of the present study was to evaluate
the effectiveness of implementing EMLA?
cream application as a routine pain-relieving
Patients and methods
Study design and patient population
The present study was a prospective, rando-
Paediatric Clinic, King Khalid University
Hospital, King Saud University, Riyadh,
Saudi Arabia over a 1-week period during
January 2012. All study participants were
healthy children, aged 2 months to 6 years,
who presented for routine immunization.
The exclusion criteria were as follows: a
history of allergy to local anaesthetics or to
any component of the EMLA?cream; a
history of uncertain drug sensitivities; active
dermatitis or an open wound at the appli-
cation site; receipt of an analgesic, anaes-
thetic or sedative <12h before the time
severe hepatic or renal disease; cardiac dis-
ease; use of class I antiarrhythmic drugs.
The study protocol was approved by the
Ethical Review Board of the College of
Medicine, King Saud University, Riyadh,
Saudi Arabia. The parents/legal guardians
of the children provided written informed
consent for their participation in the study.
Based on a computer-generated schedule,
children were randomized at study entry to
receive either ?0.5g EMLA?(AstraZeneca,
London, UK) or placebo cream (an inert
cream that could not be visually differen-
tiated from EMLA?; Bepanthen?Cream,
Bayer HealthCare, Leverkusen, Germany)
applied to an area of approximately 1cm2of
each vaccination site (the lateral region of
the right or left thigh for infants aged <1
year; the right or left deltoid for children
330Journal of International Medical Research 42(2)
aged ?1 year) before vaccination. Note that
no intervention was performed with regard
to the time of application prior to vaccin-
the area(s) of application. The applied cream
was covered with an occlusive dressing and
the time of application was recorded. The
child was subsequently enrolled in the
normal routine process of paediatrician
interview in the examination room followed
by vaccination. In the vaccination room, the
cream was wiped off and the areas were
disinfected with alcohol. The time of vaccine
administration was recorded and vaccine
injections were administered as per the rou-
tine protocol, according to the National
Arabia.10The time of application of the
cream prior to vaccination was calculated
from the moment of cream application until
the child received the first vaccine injection.
The total vaccination appointment time was
calculated from when the child arrived in the
Well-baby Paediatric Clinic until the child
received the first vaccine injection.
In the vaccination room, pain was assessed
by scoring facial expression, cry and body
(MBPS).11,12Two trained observers, who
were blinded to the
together assessed the vaccine injection-
related pain in real time. They first estab-
lished a baseline MBPS score for the 10s
period that preceded the injection, and rated
another MBPS score within 10s after the
injection. For each
between the MBPS scores after the injection
and the score at baseline were calculated.
Whether a cry occurred was noted and total
crying time was measured. Infant pain
during the vaccination was also assessed by
the nurse administering the vaccine at two
stages: at the moment of the needle prick,
and after finishing the injection and remov-
ing the needle. The nurse assessed the pain
using a 10-point visual analogue scale
(VAS), in which 0 was designated ‘no pain’
and 10 ‘worst possible pain’. Pain was
considered to be severe at scores ?7. The
reliability and validity of the VAS and
MBPS in evaluating pain associated with
vaccinations have previously been con-
firmed.12,13Adverse events were evaluated
for all children. These included local skin
reactions, such as blanching and local ery-
thema, which were assessed at the time of
dressing removal and 15min later.
All statistical analyses were performed
using the SPSS?statistical package, version
19.0 (SPSS Inc., Chicago, IL, USA) for
Windows?. Data are expressed as mean ?
SD, n of patients (%) or median (interquar-
tile range). Student’s t-test was used to
compare continuous data, Mann–Whitney
U-test was used to compare pain scores
(ordinal data), and ?2-test was used to
compare categorical data. A P-value<0.05
was considered statistically significant.
Over a 1-week period during January 2012,
239 children were seen at the Well-baby
Paediatric Clinic, King Khalid University
Hospital, for vaccination. The parents of
216 children (90.4%) agreed to participate in
the study; the other 23 children were not
enrolled in the study due to either lack of
parental consent (n¼17) or because the
injections were scheduled late after the
paediatrician interview (n¼6).
A total of 216 children who received 564
vaccination injections (median of three
injections per child) were randomly assigned
to receive either EMLA?(n¼107; 286
injections) or placebo cream (n¼109; 278
injections) for their immunization. The two
Abuelkheir et al.331
groups were similar in age, sex and type of
vaccine administered (Table 1).
Significantly fewer infants and children
cried after the vaccination in the EMLA?
group than in the placebo group: 22.4% of
children (n¼24) in the EMLA?group did
not cry at all compared with 7.3% (n¼8) in
the placebo group (P¼0.002). Total crying
time after the injection was significantly
shorter in the EMLA?group compared
with the placebo group (24.8?20.6s versus
43.3?20.5s, respectively; P<0.001). Eight
children (7.5%) in the EMLA?group cried
severely to the extent of breath-holding,
compared with 24 children (22.0%) in the
placebo group (P¼0.003).
Children’s responses to the pain asso-
ciated with vaccination injections, measured
as the difference in the pre- and postinjection
MBPS scores, were significantly lower in the
EMLA?group than in the placebo group
(difference between baseline and 0–10s after
the injection) (P<0.0001) (Table 2). The
nurse administering the vaccine rated the
children’s pain on the VAS as significantly
lower in the EMLA?group than in the
placebo group, both at the time of the needle
prickas well as
(P<0.0001 and P¼0.0001, respectively).
Significantly more children in the placebo
group experienced severe pain (pain score
?7) according to the MBPS difference, VAS
score at the time of the needle prick, and
VAS score after the injection (P<0.05 for
The median MBPS difference and the
interquartile range, as well as the minimum
and maximum values for each vaccine type
compared with the overall are presented in
Figure 1. The pain-relieving effect of the
EMLA?cream appeared least evident with
pneumococcal 13-valent conjugated vaccine
compared with other vaccines.
The mean?SD application time was
56.52?17.14min for the EMLA?group
(range 19–103min) versus 57.64?16.15min
after the injection
Table 1. Baseline characteristics of children who
participated in a prospective, randomized, double-
blind, placebo-controlled analysis of the effective-
ness of implementing eutectic mixture of local
anaesthetics (EMLA?) cream application as a rou-
tine pain-relieving strategy prior to injected vaccin-
ation appointments (n¼216).
Female 52 (48.6)
2 months23 (21.5)
4 months 16 (15.0)
6 months14 (13.1)
9 months9 (8.4)
12 months 17 (15.9)
18 months17 (15.9)
24 months7 (6.5)
4–6 years4 (3.7)
MCV 37 (12.9)
55 (19.8)52 (18.2)
17 (5.9)14 (5.0)
Baseline MBPS score 3.36?1.88
Data presented as mean?SD or n of patients (%).
DTP, diphtheria–tetanus–pertussis; HAV, hepatitis A virus;
IPV, inactivated polio vaccine; MCV, meningococcal con-
jugated vaccine; MMR, measles–mumps–rubella; PCV13,
pneumococcal 13-valent conjugated vaccine; HBV, hepa-
titis B virus; Hib, Haemophilus influenzae type B; MBPS,
Modified Behavioural Pain Scale.
No statistically significant between-group differences
(P?0.05); Student’s t-test was used to compare con-
tinuous data, Mann–Whitney U-test was used to compare
pain scores and ?2-test was used to compare categorical
332Journal of International Medical Research 42(2)
group (Table 1). Whereas the mean?SD for
the total vaccination appointment time
(measured from when the child arrived in
the Well-baby Paediatric Clinic until they
received their first vaccine injection) was
The only observed adverse event was
pallor at the site of cream application,
which was seen significantly more frequently
in the EMLA?group compared with the
placebo group (31/107 [29.0%] versus 5/109
resolved spontaneously. Neither erythema
nor swelling was observed in either group.
for thetotal study
The present study provided evidence thatthe
use of EMLA?cream for routine childhood
vaccinations was as effective as previously
reported in reducing the pain associated
with either subcutaneous or intramuscular
immunization.14–17The possible effect of
EMLA?on the immune response to live
vaccine has been assessed previously and
there was no evidence of interference from
EMLA?with vaccine immunogenicity.15,16
In the current study, a significant reduction
in VAS and MBPS scores was observed in
the EMLA?group compared with the pla-
cebo group. Both the MBPS score recorded
by the observer and the VAS score recorded
by the nurse administering the vaccines
correlated well to support the effectiveness
of EMLA?in pain relief.
The efficacy of EMLA?in reducing
overall injection pain is likely attributable
to a decrease in pain as the needle penetrates
the skin, as well as a reduction in the
underlying muscle spasm that is associated
with such pain.4,18The pain-relieving effect
of EMLA?was more pronounced at the
time of the needle prick compared with after
the needle was removed, as indicated by the
VAS score, possibly due to the limited depth
of penetration of EMLA?cream (or other
factors related to vaccine composition). The
effect of EMLA?on pain associated with
the procedures was proven by the measured
pain scores and the duration of crying. Only
local pallor at the site of cream application
was observed in just under one-third of
participants in the EMLA?group.
In this present study, the mean?SD total
vaccination appointment time from when
Table 2. Visual analogue scale (VAS) and Modified Behavioural Pain Scale (MBPS) scores before and after
injected vaccinations in children who received either eutectic mixture of local anaesthetics (EMLA?) cream or
placebo cream application prior to routine vaccination (n¼216).
Pain scale measurements
MBPS, 0–10s after injection
MBPS difference between baseline and after injection
VAS at the beginning of the injection
VAS after completing the injection
Children showing MBPS score difference ?7
Children showing VAS at the beginning of injection ?7
Children showing VAS after completing the injection ?7
Data presented as mean?SD or n of patients (%).
aMann–Whitney U-test was used to compare pain scores; ?2-test was used to compare categorical data between the two
NS, no statistically significant between-group differences (P?0.05).
Abuelkheir et al.333
the child arrived in the Well-baby Paediatric
Clinic until they received their first vaccine
injection was 57.08?16.65min for the total
study population, which was an adequate
application time for EMLA?. Although the
delayed onset of action of EMLA?cream
was cited by healthcare providers as one of
the major barriers against the routine use of
OverallHAV InfluenzaIPVMCV MeaslesMMRPCV13 Penta TetraVaricella
OverallHAV InfluenzaIPVMCV MeaslesMMRPCV13 PentaTetra Varicella
Figure 1. Modified Behavioural Pain Scale score differences for each injected vaccine type compared with
overall scores in children who received either eutectic mixture of local anaesthetics (EMLA?) cream (A) or
placebo cream (B), applied prior to routine vaccination (n¼216). Central black horizontal lines represent the
medians; extremities of the boxes show upper and lowerquartiles of data; error bars represent minimum and
maximum values. HAV, hepatitis A virus; IPV, inactivated polio vaccine; MCV, meningococcal conjugated
vaccine; MMR, measles–mumps–rubella; PCV13, pneumococcal 13-valent conjugated vaccine; Penta,
pentavalent diphtheria–tetanus–pertussis–hepatitis B virus-Haemophilus influenzae type B; Tetra, tetravalent
diphtheria–tetanus–pertussis–Haemophilus influenzae type B. The colour version of this figure is available at:
334Journal of International Medical Research 42(2)
this pain-relieving strategy for immuniza-
tion in the office setting,3,9,19the develop-
ment of a protocol for cream application by
the nurses on the child’s arrival helped to
overcome this obstacle. In addition, the
mean total vaccination appointment time
after administering the EMLA?cream did
not differ markedly from the mean?SD
waiting time at the King Khalid University
Hospital, which was previously found to be
47.34?20.47min based on performance
monitoring (personal communication). It
is expected that as vaccination nurses
become more familiar with the EMLA?
application procedures, the time to first
vaccination will decrease further toward
the hospital’s baseline measurement time of
Taddio et al.20reported a comparable
mean?SD waiting time of 41.6?28.7min
for childhood vaccination appointments in
eight outpatient primary care clinics. This
waiting time included the general waiting
room time plus examination room time
before the actual vaccine injection, without
implementing any extra pain-relieving strat-
egy. Therefore, whenever the typical wait
time for a vaccine appointment exceeds
30min, application of local anaesthetic
could be incorporated within the process of
vaccine injection without substantially pro-
longing the duration of the visit.
Studies have focused on evaluating pain
associated with specific vaccine types in a
particular age group.14–16In contrast, the
present study included all eligible children
who presented to the Well-baby Paediatric
Furthermore, the pain associated with all
vaccine injections given to the children was
assessed. Thus, this may increase the gener-
alizability of the present study for imple-
menting EMLA?cream application as a
routine pain-relieving strategy in clinical
vaccination practice. However, because the
present study was conducted in a relatively
small number of children from a single
centre, these findings may warrant further
research in this regard.
The present study showed that infants
and children receiving pre-treatment with
EMLA?cream before their routine vaccin-
ations manifested significantly lower pain
scores compared with the placebo group,
with little increase in the mean time between
child arrival at the clinic and first vaccine
EMLA?cream be used routinely before
advantages of alleviating the child’s pain
and their parents’ anxiety levels.
Declaration of conflicting interest
The authors declare that there are no conflicts of
The authors are thankful to the Deanship of
Riyadh, Saudi Arabia for supporting the work
through a Research Group Project Grant (RGP-
The authors are thankful to the Deanship of
Riyadh, Saudi Arabia for supporting the work.
We also extend our thanks to the nursing staff at
the Well-baby Paediatric Clinic, King Khalid
University Hospital, King Saud University,
Riyadh, Saudi Arabia.
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