Linda Ikuta, MN, RN, CCNS, PHN ❍ Section Editor

Foundations in Newborn Care

2.5
HOURS
Continuing Education

The Combined Use of Sucrose

and Nonnutritive Sucking for
Procedural Pain in Both Term
and Preterm Neonates
An Integrative Review of the Literature
Kelli Ann Naughton, MSN, NNP-BC

ABSTRACT
Many agents, both pharmacologic and nonpharmacologic, have been studied to alleviate neonatal
pain, and the research is extensive. The 2 most commonly studied nonpharmacologic agents studied
have been sucrose and nonnutritive sucking (NNS). There is increasing evidence that the synergistic
effect of sucrose and NNS is more effective than the effect of sucrose or NNS alone. The purpose of
this integrative review of the literature was to determine whether there is a relationship between the
synergistic effect of combining sucrose and NNS administered before and during painful procedures,
and reducing procedural pain in both preterm and term neonates. This integrative review indicates
that the combination of sucrose and NNS is a safe, effective, and clinically significant means of
providing procedural pain relief in neonates, both term and preterm.
Key Words: neonate, nonnutritive sucking, nonpharmacologic, pain management, preterm neonates,
procedural pain, sucrose, term neonates

T
he recognition, management, and clinical
importance of neonatal pain and stress have
been slow to progress over time. During the
1970s and 1980s, there were many achievements
and breakthroughs made in increasing the surviv-
ability of critically ill neonates. We are now able to
help neonates of increasingly lower gestational age
and more advanced diseases survive to discharge
from the neonatal intensive care unit (NICU). During
Author Affiliation: Mount Sinai Medical Center, New
York, SUNY Stony Brook University School of Nursing,
New York, and Steven and Alexandra Cohen Children's
Medical Center of New York, New Hyde Park.
The authors have disclosed that they have no financial
relationships related to this article.
Correspondence: Kelli Ann Naughton, MSN, NNP-BC,
Cohen Children's Medical Center of New York,
Neonatal/Perinatal Medicine, 269-01 76th Ave, Suite
344, New Hyde Park, NY 11040 (knaughton@nshs.edu).
Copyright © 2013 by The National Association of
Neonatal Nurses
DOI: 10.1097ⲐANC.0b013e31827ed9d3
this time and in earlier decades, the effects of noxious
stimuli in neonates were being researched and begin-
ning to become better understood. During the 1990s,
there was a push for more developmental care to be
instituted into the care plans of critically ill neonates.
Along with developmental care initiatives, new ther-
apies, technologies, and techniques aimed at reduc-
ing unnecessary stress and pain in neonates were
developed. These developments continue today.1–3
The International Association for the Study of
Pain defines pain as “an unpleasant sensory and
emotional experience associated with actual or
potential tissue damage, or described in terms of
such damage.”1(p124),3(p61),4(p106),5(p3) Being unable to
communicate verbally in no way negates the possi-
bility that an individual is experiencing pain and is
in need of appropriate pain-relieving treatment.1,4,5
This definition can be applied to neonates because
research suggests that neonates, full-term and pre-
term, display both physiologic and behavioral cues
to pain and stress and these cues are valid indicators
of neonatal pain.5 When discussing pain in neonates,
the term nociception is often used because it better

Advances in Neonatal Care • Vol. 13, No. 1 • pp. 9-19 9

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 10 Naughton
describes the experience of pain in neonates. One
researcher4 showed preference for the term nocicep-
tion because it refers to “the physiologic process of
transduction, transmission, perception and modula-
tion of specific stimuli through the nervous system
rather than only the behavioral and social compo-
nents of pain.”(p106) The author4 later stated “the
detection of a noxious stimulus and the transduction
and transmission of information about the presence
and the quality of that stimulus from the site of stim-
ulation to the brain.”(p106) Another researcher1
described the term nociception as being “used to
describe the effects of a stimulus independent of any
judgment of higher consciousness, memory or
possible emotional effects or suffering.”(p124)
In the developing fetus, the anatomic maturation
of the nociceptive pathways from the peripheral
receptors to the cerebral cortex is usually complete
by the middle to the end of the second trimester.
Neonates manifest similar physiologic changes in
their endocrine and metabolic systems, cardiovascu-
lar and respiratory systems, and behavioral
responses, in response to pain and distress as older
children and adults do.1–3,5 However, newborns have
been shown to exhibit a more prolonged stress
response than adults as measured by an increase in
cortisol.
Nociception is measured by various biologic com-
ponents that assess pain as opposed to assessing only
external, physical signs of pain. A group of research-
ers4 defines several biologic markers for stress and
therefore pain in the neonate. Neonates display a
change in hormonal response, including an increase
in the catecholamines, epinephrine and norepineph-
rine, cortisol levels, and ␤-endorphins. The produc-
tion of insulin is suppressed and glucagon is released
from the pancreas. Growth hormone and prolactin
are secreted more frequently when pain manage-
ment is not used in neonates.4 In addition, nocicep-
tion is measured by increased heart rate, blood pres-
sure, and respiratory rate, intracranial pressure and
sweating, and decreased oxygen saturation and
vagal tone. A neonate’s behavioral response to pain
or nociception is similar to an adult’s but is more
exaggerated. These behavioral responses to pain
include crying, facial grimacing, chin quivering, eye
squeezing, nasolabial furrowing, taught tongue,
open andⲐor stretched mouth, lip purse, and agita-
tion alone or in combination.1–5 Another researcher1
suggests that newborns may experience an increased
sensitivity to pain and preterm neonates may have a
more pronounced sensitivity than term neonates.
Pain in the neonate has both short- and long-term
adverse effects on physical and developmental
outcomes, which are more pronounced in the very-
low-birth-weight (VLBW) preterm neonate. In the
short term, the physiologic signs of pain and dis-
tress, including increased heart rate, blood pressure,
Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC200347.indd 10
respiratory rate, and crying, can be physiologically
detrimental in the VLBW preterm neonate. This
instability alters metabolic demand and oxygenation
and may contribute to intraventricular hemorrhage.
In the older preterm and full-term neonates, pain
and distress, in the short term, can manifest itself in
sleep and feeding disruptions and disruptions in
interaction patterns.1,3,5 There are conflicting data as
to the long-term effects repeated painful stimuli as a
neonate. Some older infants and children have exag-
gerated responses to painful stimuli, while others
have decreased responses.1,3,4
There are multiple lines of evidence showing that
neonates who are hospitalized undergo multiple
painful procedures during their stay. Even full-term
neonates in the standard newborn nursery are subject
to painful procedures. These procedures are medi-
cally necessary for their care but may become quite
extensive. These procedures include—but are not
limited to—intubation and mechanical ventilation,
nasal, tracheal, and nasopharyngeal suctioning, heel
sticks, intravenous catheter insertion, nasogastric
tube insertion, arterial puncture, lumbar puncture,
venipuncture, central catheter insertion, intramuscu-
lar injections, chest tube insertion, circumcision, and
surgical interventions. Many of these procedures are
routine for certain disease states or are routine new-
born care. Quite often these procedures are per-
formed multiple times to account for failed
attempts.2,5,6
Many agents, both pharmacologic and nonphar-
macologic, have been studied to alleviate neonatal
pain, and the research is extensive. The 2 most com-
monly studied nonpharmacologic agents have been
sucrose and nonnutritive sucking (NNS).1,2,4,5,7
Although these agents have been extensively studied,
there is a gap in knowledge as to the appropriate
dosing of sucrose and in the safety and efficacy of
long-term repeated doses of sucrose. There is increas-
ing evidence that the synergistic effect of sucrose and
NNS is more effective than the effect of sucrose
alone. Numerous studies have also shown that
although there is evidence-based research regarding
sucrose and NNS, they are not always used in rou-
tine neonatal care and pain management. This may
be due to the gaps in knowledge stated previously.
This integrative review of the literature studies the
body of evidence surrounding the use of combining
2 nonpharmacologic techniques for reducing neona-
tal pain, sucrose in combination with NNS. For this
integrative review of the literature, reports were
included that studied both preterm and full-term
neonates, and various measures of nonpharmacologic
pain management that included sucrose and NNS as
variables. No exclusions were made on the basis of
year of publication or country in which the studies
were conducted but only articles printed in English
were included. Both qualitative and quantitative
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18/01/13 10:47 PM

studies were included. The purpose of this integra-
tive review of the literature was to determine whether
there is a relationship between the synergistic effect
of combining sucrose and NNS administered before
and during painful procedures, and reducing proce-
dural pain in both preterm and term neonates.
METHODS
In conducting this integrative review of the litera-
ture, it is necessary to search multiple databases
using several key words and key word combina-
tions. This search was done solely using computer
databases. This author used both the SUNY Stony
Brook HSC Library and the library in the hospital
and medical school where employed, which is the
Mount Sinai Levy Library, as well as an Internet
search. The Internet search allowed for identifica-
tion of what articles were at least in part relevant to
the topic and then those articles were searched for
using various databases in these libraries. For the
relevant articles that were obtained, a citation search
was conducted to attempt to find more relevant arti-
cles. Initially, no exclusion criteria were imposed,
except for searching for only English language
research, regardless of the country of origin, and the
availability of the article in full text. In further con-
ducting the search, this author decided to exclude
articles specifically related to the use of sucrose and
NNS for neonatal pain for specific procedures, such
as circumcision and retinopathy of prematurity
examinations because a more general body of
research is desired, as opposed to research on specific
procedures. If the article contained these specific
procedures as well as other procedures such as heel
lance or venipuncture, they were included. All
research types, quantitative, qualitative, and review,
were considered for inclusion. The vast majority of
TABLE 1. Databases Searched and Key Words Used to Show Search Results
Neonatal
Neonatal Procedural
Database Pain
CINAHL 729
PubMedⲐMEDLINE 6 228
ISI Web of Knowledge–Web of 1 591
Science
Cochrane Database 31
Cochrane Database of Systemic 1a
Reviews
PSYCHinfo 5 839
Google Scholar 210 000
a
This article is the same one found for all key words.
Advances in Neonatal Care • Vol. 13, No. 1
Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC200347.indd 11
Sucrose and NNS for Procedural Pain in Neonates 11
research available is quantitative as well as several
reviews. There were no limits placed on the year of
publication of the research to allow for primary
research. The following databases were searched:
CINAHL, PubMedⲐMEDLINE, and ISI Web of
Knowledge–Web of Science, The Cochrane Database
including the Cochrane Database of Systemic
Reviews and PSYCHinfo, as well as Google Scholar.
The key words used were “neonatal,” “pain,”
“procedural pain,” “sucrose,” and “nonnutritive
sucking” in various combinations.
The databases searched and the initial search
results for each are depicted in Table 1. The Google
Scholar search was more of a guide to see the various
articles that may be available and produced very
large numbers of results that were unmanageable. In
Google Scholar, for the key word combination
“neonatal pain AND sucrose AND nonnutritive
sucking,” results were sorted by relevance, the first
100 articles scanned and the most relevant articles
marked to determine whether these articles were
also found in the various databases. Because of the
often very large number of results in each database
for the key word combinations “neonatal pain” and
“neonatal procedural pain,” the results were sorted
by relevance to the key words and availability of full
text. This still produced a large number of results, so
these were scanned through the first 100 articles
after sorting and the most relevant articles were
placed into a folder for these key words. The searches
of the key word combinations “neonatal pain and
sucrose,” “neonatal pain and nonnutritive sucking,”
and “neonatal pain and sucrose and nonnutritive
sucking” yielded more manageable search results.
For each database and each key word combination,
the results were sorted by relevance and availability
of full text. The most relevant of these articles were
placed in a second folder. Both folders were compared
Neonatal Neonatal Pain
Neonatal Pain AND AND Sucrose AND
Pain AND Nonnutritive Nonnutritive
Pain Sucrose Sucking Sucking
51 62 7 4
150 176 27 19
133 123 16 12
0 3 1 1
1a 1a 1a 1a
4 1 0 0
24 600 12 400 808 356
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 12 Naughton
to determine whether they contained the same arti-
cles. There were a total of 75 relevant articles that
were then placed in a third folder, which combined
the first 2 folders. On further review of the 75 arti-
cles, it was noted that about 50 of the articles
researched only the use of sucrose for neonatal pain
relief and the safety and efficacy of the use of sucrose.
Since this literature review is studying the combina-
tion of sucrose and NNS for neonatal pain relief, the
results were further narrowed down in this folder to
25 articles. In the search of full-text articles within
this folder, 22 of the 25 articles were able to be
obtained. Each of the 22 articles was obtained and
reviewed. For the article found from The Cochrane
Database of Systemic Reviews, only the section
pertaining to the use of sucrose and NNS in combi-
nation was reviewed as the article is upward of 160
pages and discusses many different methods of
relieving neonatal pain. After careful review of each
of these articles, it was decided that only research
that explored the combination of sucrose and NNS
was to be included so as to satisfy the purpose of this
integrative review. Studies that did not include this
combination were excluded. Of the 22 articles,
10 articles were chosen for inclusion for analysis and
interpretation in this integrative review.
ANALYSIS AND INTERPRETATION
The purpose of this integrative review of the literature
was to determine whether there is a relationship
between the synergistic effect of combining sucrose
and NNS administered before and during painful
procedures, and reducing procedural pain in both
preterm and term neonates. This integrative review
studies 10 research articles, including quantitative and
review research (see Tables 2 and 3). Seven of these
articles fall into the category of quantitative or exper-
imental and 3 of these articles are reviews of the
literature. The articles chosen for inclusion are
exhaustive of the research available for the specific
inclusion criteria for this integrative review. The
following section discusses these articles in accor-
dance with the research purpose.
Some of the earliest research, dating back to only
1990,8 focused on the different pathways of orogus-
tatory and orotactile stimulation using sucrose and
pacifiers (Table 2). One of the 3 experiments included
sucrose infused through a pacifier that produced a
calming effect compared with water infused through
a pacifier and these results reached statistical signifi-
cance. In this study, statistical significance was also
reached in another of the experiments that tested
sucrose administration with water administration. A
pacifier alone was found to calm but did not have a
lasting effect. This research did not study a specific
“painful” stimulus, but it used the stimulus itself to
conduct the experiments, nor did it use a reliable,
Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC200347.indd 12
valid tool for measuring “pain” or “discomfort”
(Table 2). This study demonstrated high interrater
reliability and claimed randomization but did not
state the method used to employ this randomization.
The findings of this study show that orogustatory
and orotactile stimulation operate through different
pathways to calm a 1- to 3-day-old full-term infant.
Suggestions were made to use this study to guide
future research on how ingestion and contact
influence coping with stress and pain in infants.8
There was a span of 9 years noted between the
earliest researchers8 and the next published article
studying the combination of sucrose and NNS. This
is reflective of the lack of substantive research on
neonatal pain itself before the 1990s. This study9
(Table 2) studied how taste- and sucking-induced
analgesia combated pain in healthy term neonates
during a mandatory heel stick procedure and blood
collection. This study used crying, grimace, and
heart rate to measure pain during the heel stick pro-
cedure and blood collection.9 With the exception of
heart rate, the tools to rate pain are not clinically
reliable or valid. Heart rate is not a clinically reliable
or valid tool, but neonatal response to pain can be
seen by an increase in heart rate, so physiologically
heart rate can indicate a response to a painful proce-
dure. This experiment used 40 subjects randomized
into 1 of 4 study groups. There is some question
raised about the actual randomization procedure.
This is because the study stated that 17 of the sub-
jects were exclusively breastfed, for 8 of the subjects
it was not their first heel stick, and 10 subjects were
circumcised the previous day, and for each, these
infants were distributed equally among the groups
with no mention of assignment of random study
numbers. There was some control for variability
because one phlebotomist was used for 36 of the
40 heel stick procedures and blood collection. This
study found the synergistic effect of sucrose and
NNS to yield remarkable analgesia.9
French researchers10 (Table 2) studied the syner-
gistic effect of sucrose and pacifiers, using the behav-
ioral acute pain rating scale for neonates, Douleur
Aique du Nouveau-ne (DAN). This scale had recently
been validated as a clinically valid scale. This was a
randomized and controlled study, and the sampling
procedure and the randomization procedure were
clearly explained. This study found that the associa-
tion of sucrose and a pacifier showed a trend toward
lower pain scores compared with a pacifier alone,
but this did not reach statistical significance.10 This
study acknowledged its limitations and weaknesses
such as the observer being blinded to the solution
administered but not to the use of a pacifier since this
was impossible in this study, its small sample size,
the design of the study being only able to detect a
2-point difference in the DAN scores and lacked
power to detect a 1-point difference, and the DAN
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ANC200347.indd 13
TABLE 2. Evidence for Quantitative Studies Regarding the Use of Sucrose and Nonnutritive Sucking (NNS) for Procedural
Pain in Neonates
Study TypeⲐ
Author(s)a Design Main Purpose(s) Procedure Sample Treatment Control Pain Tools Results
Smith et al8 Randomized To determine the Stimuli 3 trials 1. 0.1 mL of 14% 1. 0.1 mL of Cryingb and 1. Sucrose eliminated
Experimental calming effect of 1. SucroseⲐ Total n ⫽ 92 sucrose water time spent crying—statistically
sucrose, pacifier, or water full-term 2. Compared 2 2. No control. crying significant
combination instillation infants groups 2. Sucrose calmed more
3. Pacifier to
compared with effectively than pacifier
2. Pacifier GA ⬎ 38 wks a. 0.1 mL of 14% infuse 0.1 mL
water andⲐor as pacifier had no
1. n ⫽ 16 sucrose over 2, of water
pacifier lasting effect
6, or 10 min
2. n ⫽ 56
b. Pacifier held for 3. Sucrose through
3. n ⫽ 20 pacifier calmed and
2, 6, 10, or

Advances in Neonatal Care • Vol. 13, No. 1

14 min water did not—
statistically significant
3. pacifier infuse 0.1
mL of 14% sucrose
Blass and Randomized 1. To identify the basis Heel stick and Full-term new- 4 groups: No control Cryingc 1. Sucking is analgesic
Watt9 experimental of sucking induced blood borns 1. 2 mL of 12% Grimacingd when suck rate exceeds
analgesia collection n ⫽ 40 sucrose 30 sucks per minute
HR
2. Evaluate how taste Randomly 2. 2 mL of water 2. Combination of sucrose
and sucking-induced assigned to and NNS shows
3. Pacifier dipped
analgesia combine 1 of 4 treat- remarkable analgesia
in water
to combat pain ment groups 3. Facial grimace is an
4. Pacifier dipped
3. To determine if (n ⫽ 10) accurate index of
in 12% sucrose
facial grimacing is diminished pain
an accurate index
of diminished pain
Carbajal Randomized 1. Assess and com- Venipuncture 150 full-term 1. Placebo (2 mL of No treatment DANe 1. The analgesic effects of
et al10 prospective pare the analgesic infants, water) concentrated glucose,
Controlled effects of orally n ⫽ 25 in 2. 2 mL of 30% sucrose, and pacifiers
administered glu- each of glucose are clinically apparent
cose, sucrose, and 6 groups in newborns
3. 2 mL of 30%
pacifiers 2. Pacifiers are more effec-
sucrose
2. To determine the tive than sweet solutions
4. Sucking on a pac-
synergistic effect of 3. Sucrose ⫹ pacifier tend
ifier
sucrose and

Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
to lower pain scores
Sucrose and NNS for Procedural Pain in Neonates

pacifier 5. 2 mL of 30%
than pacifier alone but
sucrose ⫹ pacifier
not statistically
significant
13

(continues)

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 14

TABLE 2. Evidence for Quantitative Studies Regarding the Use of Sucrose and Nonnutritive Sucking (NNS) for Procedural

ANC200347.indd 14
Pain in Neonates, Continued
Study TypeⲐ
Author(s)a Design Main Purpose(s) Procedure Sample Treatment Control Pain Tools Results
Stevens Prospective ran- To compare the Heel stick 122 VLBW neo- 4 interventions in Infants served as PIPP A combination of sucrose
Naughton

et al11 domized cross- efficacy of nate GA ⫽ random order, their own and NNS (delivered as
over trial developmentally 27–31 wks 1 control and control a pacifier dipped in
sensitive ⬍ 28 d old 3 treatments: Control condition: sucrose) produced the
interventionsf with 1. Prone Standard NICU most efficacious means
standard NICU positioning careg of pain reduction for
careg for single procedures in
2. Pacifier with
decreasing this VLBW population
water
procedural pain
3. Pacifier with
24% sucrose
Akman Prospective To assess and Heel stick 138 healthy Group 2 mL of sterile NFCS Group 4 had lower pain
et al12 Double blind compare the full-term 1. Dextrose 12.5% water and scores and crying time
analgesic effects of neonate GA 2 mL than group 2 but was
Controlled crying
orally administered ⫽ 37-42 wks not statistically
2. Dextrose 12.5% timeh
sucrose, dextrose, significant concluding
2 mL ⫹ pacifier
dextrose ⫹ pacifier, that sweet solutions
sucrose ⫹ pacifier, 3. Sucrose 12.5% combined with pacifier
and sterile water, 2 mL provide superior pain
during minor 4. Sucrose 12.5% relief compared with
painful procedures 2 mL ⫹ pacifier sweet solutions alone
in neonates
Gibbins Randomized To compare the Heel lance 190 neonates 1. Sucrose 24% Sterile water 2 PIPP PIPP scores were
et al13 controlled efficacy and safety stratified for 0.5 mL ⫹ NNS mL ⫹ NNS significantly lower in
of 0.5 mL of 24% GA 2. Sucrose 24% 2 the sucrose ⫹ NNS
sucrose with a calculated mL via syringe group than sucrose
pacifier (NNS) with based on alone or sterile water ⫹
sucrose alone or PIPP score: NNS. There were no
sterile water and 27–31; 6Ⲑ7; significant differences
NNS for 32–35; 6Ⲑ7; in PIPP scores between
decreasing 36–43 wks sucrose alone and
procedural pain sterile water ⫹ NNS.
associated with The combination of
heel lances in

Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
sucrose ⫹ NNS is the
preterm and term most efficacious
neonates intervention for single-
heel lances

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(continues)

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ANC200347.indd 15
TABLE 2. Evidence for Quantitative Studies Regarding the Use of Sucrose and Nonnutritive Sucking (NNS) for Procedural
Pain in Neonates, Continued
Study TypeⲐ
Author(s)a Design Main Purpose(s) Procedure Sample Treatment Control Pain Tools Results
Elserafy Randomized To determine the Venipuncture 36 preterm Each neonate No treatment— PIPP and Sucrose 24% ⫹ pacifier
et al14 prospective analgesic effects of neonate GA received each of standard NICU crying resulted in the lowest
Double blinded sucrose versus ⫽ 27–36 6 regimes over careg time pain score for all
sterile alone or weeks 15 d groups for all

Advances in Neonatal Care • Vol. 13, No. 1

Controlled
with a pacifier in 1. Sterile water measurements and the
preterm neonates 0.5 mL ⫹ pacifier results were statistically
significant. The other
2. Sterile water
groups were not found
0.5 mL
to be statistically
3. Sucrose 24% significant
0.5 mL ⫹ pacifier
4. Sucrose 24%
0.5 mL
5. Pacifier alone

Abbreviations: DAN, Douleur Aique du Nouveau-ne; GA, gestational age; HR, heart rate; NFCS, neonatal facial coding system; NICU, neonatal intensive care unit;
NNS, nonnutritive sucking; PIPP, premature infant pain profile; VLBW, very-low-birth-weight neonates.
a
Listed chronologically.
b
Defined as a crying sound and a crying face.
c
Defined as presence of audible crying vocalizations.
d
Defined as a furrowing of the brow and eye squinting.
e
DAN: Behavioral acute pain rating scale for neonates.
f
Prone positioning, pacifier with water or pacifier with sucrose.
g
SupineⲐside-lying positioning with no pacifier or sucrose or other nursing intervention (stroking, rocking, talking, and music).
h
Defined as the duration of crying within 3 minutes.

Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
Sucrose and NNS for Procedural Pain in Neonates
15

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 16 Naughton
scale not being able to assess the degree of the per-
ception of pain. There is strength in that the study
employed a clinically valid tool. This study finds that
sucrose and a pacifier, among other interventions,
are safe and effective ways to reduce pain in neonates
during minor painful procedures.10
In 1999, a group of researchers11 (Table 2) were
the first to study developmentally sensitive interven-
tions (including a pacifier dipped in sucrose) for pro-
cedural pain in VLBW preterm neonates. These
VLBW preterm neonates are rarely studied and most
likely experience the most amount of procedural
pain in the course of their NICU stay. In this trial,
each infant served as its own control because they
received all 4 of the interventions in random order.
This study clearly defined its standardization and
randomization procedures and used the Premature
Infant Pain Profile (PIPP) pain tool, a clinically reli-
able and valid tool, to measure procedural pain in
these VLBW preterm neonates. This study identified
its limitation in that these researchers only evaluated
for pain-reducing or relieving effects during a single
painful procedure, for which they implied that and
recommended future research on the safety and
efficacy of sucrose and NNS in repeated doses and
over time. This study found that a pacifier dipped in
sucrose, of all the other variables tested, was the
most efficacious means of pain reduction for a single
painful procedure.11
A Turkish study12 (Table 2) examined sucrose and
dextrose with and without a pacifier and compared
the analgesic effects for minor procedural pain in
healthy term neonates. This study tools were crying
time and pain scores using the Neonatal Facial
Coding System before, during, and after a heel
lance. The study was randomized, but the random-
ization process was not explained. This study
included the limitation that the observer was not
blinded to the administration of a pacifier to the
infants but this blinding was not possible in the
study. The researchers found that of all interven-
tions made, sucrose followed by a pacifier had lower
pain scores and crying time than dextrose followed
by a pacifier, but this difference was not statistically
significant, concluding that an enhanced analgesic
effect was obtained with a combination of either
sugar with a pacifier.12
Another group of researchers13 conducted a ran-
domized controlled trial, using the Gate Control
Theory of Pain, whose purpose was to compare the
safety and efficacy of sucrose with NNS to sucrose
alone, controlled by water and NNS, for decreasing
procedural pain associated with heel lances in both
term and preterm neonates. This trial used the PIPP,
a clinically reliable, valid, and widely used pain-rating
tool. The PIPP scores according to gestational age
due to the assumption that premature neonates can
actually feel more pain and are not yet developmentally
Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC200347.indd 16
able to show many of the classic pain symptoms seen
in neonates. These researchers13 were very specific in
describing their sample size and collection methods,
standardization, as well as their randomization
procedures and showed high interrater reliability.
This study also assessed for adverse effects of the
procedure, which was not seen in many of the other
studies included in this integrative review. These
researchers13 recognized that a limitation of this
study was the lack of data on the ability to suck effi-
ciently. This trial found that the PIPP scores were
significantly lower in the sucrose with NNS group
than the sucrose alone and sterile water with NNS,
whose scores showed no significant difference in
PIPP scores.
A 2009 Saudi Arabian study14 researched the
analgesic effects of sucrose versus water alone or
with a pacifier in preterm neonates. They used the
PIPP as the pain-rating tool due to its clinical reli-
ability and validity, as well as crying time, before,
during, and after a venipuncture procedure. This
trial used a control of standard care or no treatment.
This study did not clearly describe its randomization
and standardization procedures. This study resulted
in the combination of sucrose and NNS having the
lowest pain scores of all groups for all measure-
ments, which was found to be statistically signifi-
cant. They found no side effects in the administra-
tion of sucrose to preterm neonates. This study
implies that the synergistic effect of the combination
of sucrose and NNS is statistically and clinically
effective and safe intervention for relieving pain
during simple procedures in term and preterm
neonates. Future research was recommended.14
Three review studies were chosen for inclusion for
this integrative review. These reviews were extensive
and discussed numerous types of pain relief measures
for neonates, so the results are discussed here with
reference to the specific purpose of this integrative
review. Two authors15 reviewed the literature con-
cerning the use of sucrose with preterm infants. The
literature included physiologic mechanisms for
sucrose action, current recommendations for sucrose
use, and a critique of published studies involving the
use of sucrose with preterm neonates (Table 3). They
identified the limitation that less research has been
done concerning preterm neonates and recom-
mended additional research to determine the most
effective approaches for the administration of
sucrose, to examine the effectiveness with additional
types of painful procedures as most research has
been conducted using heel sticks and venipuncture,
and to examine the effects of the long-term, repeated
use of sucrose. The review concluded that the admin-
istration of oral sucrose is effective as a simple and
safe method of pain relief for neonates, and that oral
sucrose may be combined with NNS to provide
significant pain relief.15 Another article16 reviewed
www.advancesinneonatalcare.org
18/01/13 10:47 PM
ANC200347.indd 17
TABLE 3. Evidence for Included Reviews Regarding the Use of Sucrose and NNS for Procedural Pain in Both Term and
Preterm Neonates
Study:
Author(s)a Purpose
Mitchell and To review the literature concerning the Studies have demonstrated that the administration of
Waltman15 use of oral sucrose with preterm
infants. The literature review includes pain relief for infants during painful procedures. Oral
physiologic mechanisms of sucrose
action, current recommendations for
sucrose use, and a critique of
published studies involving the use
of sucrose with preterm infants.
Advances in Neonatal Care • Vol. 13, No. 1
Tsao et al16 To provide an overview of the literature
of CAM approaches for pain and
distress related to medical
procedures among infants up to 6
weeks of age. The focus of this article
is to review the empirical literature
on sucrose with and without NNS on
minor procedural pain in infancy.
Stevens et al17 To determine the efficacy, effect of
dose, method of administration, and
safety of sucrose for relieving proce-
dural pain as assessed by physiologi-
cal (heart rate, respiratory rate, satu-
ration of peripheral oxygen in the
blood [Spo2], transcutaneous
oxygen and carbon dioxide [gas
exchange measured across the
skin—Tcpo2, Tcpco2]) andⲐor behav-
ioral pain indicators (cry duration,
Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
proportion time crying, facial actions)
andⲐor composite pain scores.
18/01/13 10:47 PM
Main Findings Recommendations
Additional research is warranted to
oral sucrose is effective as a simple and safe method of (1) determine the most effective
approaches for the administration
sucrose may be combined with NNS to provide of sucrose, (2) examine the
significant pain relief. effectiveness with additional
types of painful procedures as
most research has been done
using minor procedures such as
heel sticks or venipuncture, and
(3) examine the effects of long-
term, repeated use of sucrose.
On the whole, it appears that sucrose, NNS, and sweet- Further well-controlled
ened solutions hold considerable promise for reducing investigations using validated
infant procedural pain. The findings extend to both behavioral pain measures are
minor (eg, heel stick) and major (eg, circumcision) pro- called for.
cedures. It appears that sucrose administered before a
procedure onⲐwith a pacifier to induce NNS may be the
most consistent form of pain relief.
Exhaustive review that includes the characteristics of both The recommendation, based on this
the included and excluded studies. Included 44 studies, review, is that 0.012 to 0.12 g of
22 on term neonates and 20 on preterm neonates and 2 sucrose should be administered
on both term and preterm neonates. This review approximately 2 min before
determined that sucrose is safe and effective for single-heel lances and considered
reducing procedural pain for single events. Sucrose for use with venipunctures for
reduces procedural pain with minimal to no side pain relief in neonates. Other
effects. Small doses of 24% sucrose (0.01-0.02 g) are methods of pain relief, including
efficacious in VLBW infants while larger doses NNS, should be considered in
(0.24-0.50 g) reduce the proportion of time crying in combination with sucrose to
term infants. A dose range of sucrose for reducing significantly reduce or eliminate
procedural pain in neonates was identified as 0.012 to pain in this population.
Sucrose and NNS for Procedural Pain in Neonates
0.12 g (0.05-0.5 mL of 24% solution).
(continues)
17
 18 Naughton

complementary and alternative medicine approaches

needed. Sucrose use in extremely

andⲐor ventilated neonates needs

for distress and pain related to medical procedures

neonates and the use of sucrose

Further investigation on repeated

pharmacologic interventions is

low-birth-weight and unstable

among neonates up to 6 weeks of age (Table 3). The

(eg behavioral, physical) and

administration of sucrose in
focus was to review the empirical literature on

in combination with other

TABLE 3. Evidence for Included Reviews Regarding the Use of Sucrose and NNS for Procedural Pain in Both Term and

Recommendations
sucrose with and without NNS for procedural pain
in infancy. This review recognized that in many stud-

nonpharmacologic
ies, validated behavioral pain tools were not used

to be addressed.
and recommended future well-controlled investiga-
tions using validated behavioral tools. Their findings
were that on the whole, sucrose, NNS, and sweet-
ened solutions hold considerable promise for reduc-
ing neonatal procedural pain. The findings of this
study extend to both minor (heel stick) and major
(circumcision) procedures. Their findings also

Abbreviations: CAM, complementary and alternative medicine; NNS, nonnutritive sucking; VLBW, very low birth weight.
revealed that it appeared that sucrose administered
before a procedure on a pacifier to induce NNS may
should be considered in combination with sucrose to
studies. Other methods of pain relief, including NNS,

be the most consistent form of pain relief.16 An

inconsistency in effective sucrose dosage among
An optimal dose could not be identified because of

extensive Cochrane review17 was also included in

this integrative review to determine whether the
significantly reduce or eliminate pain in this

findings of this review were similar or not to the

Cochrane review. The purpose of this Cochrane
review was to determine the efficacy, effect of dose,
and safety of oral sucrose for relieving procedural
Main Findings

pain in neonates (Table 3). This review found that

sucrose is safe and effective for reducing procedural
pain for single events with minimal to no side effects.
An optimal dose could not be determined because of
the inconsistencies in effective sucrose dosing among
studies. They also found that other pain-relieving
measures, such as NNS, should be considered in
combination with sucrose to significantly reduce or
population.

eliminate pain in neonates.17 This extensive Cochrane

review recommends further research on repeated
administration of sucrose in neonates and the use of
sucrose in combination with other nonpharmaco-
logic (eg behavioral, physical) and pharmacologic
interventions. Sucrose use in extremely low-birth-
weight and unstable andⲐor ventilated neonates also
needs to be investigated.17

DISCUSSION
The purpose of this integrative review of the litera-
Purpose

ture is to determine whether there is a relationship

Preterm Neonates, Continued

between the synergistic effect of combining sucrose

and NNS administered before and during painful
procedures, to reduce procedural pain in neonates.
All of the studies included in this review researched
the combination of sucrose and NNS to determine
Listed chronologically.

whether there was a synergistic effect between the 2

nonpharmacologic means of procedural pain relief.
With the exception of 2 studies, sucrose in combina-
tion with NNS for the neonatal population provided
the most effective and significant procedural pain
Author(s)a

relief. The Cochrane review17 is the most recent

study and recommended that sucrose combined with
Study:

other pain-relieving methods, such as NNS, be used

for procedural pain in neonates.
a

www.advancesinneonatalcare.org
Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.

ANC200347.indd 18 18/01/13 10:47 PM


The calming and pain-relieving effects of sucrose
are thought to be mediated by endorphin-releasing
pathways activated by sweet taste. The orogustatory
effects of sucrose have been demonstrated in animal
studies and in preterm and term human neonates
during painful procedures.18 In contrast to sucrose,
the analgesic effects of NNS are hypothesized to be
activated through non–endorphin-releasing path-
ways by orotactile stimulation. The combination of
orogustatory effects and orotactile effects appears to
be superior in the management of neonatal pain.8
The evidence is sufficient to support the efficacy of
combining the 2 interventions for procedural pain
relief in neonates.18 This integrative review supports
the practice of a synergistic effect utilizing both
sucrose and NNS for procedural pain relief in term
and preterm neonate, as a safe and effective means
of providing procedural pain relief.
LIMITATIONS, RECOMMENDATIONS,
AND IMPLICATIONS
This integrative review of the literature is limited in
that it included only studies that tested the combina-
tion of sucrose and NNS. Although this was the pur-
pose of the review, other sweet solutions, such as
dextrose or glucose, were not studied. This review is
also limited in that the included studies used several
different doses, concentrations, and intervals of dos-
ing for sucrose. Further research is warranted to
determine the most safe and effective concentration,
dose, and interval of dosing of sucrose. Of all the
studies researched, both included and excluded from
this review, none discussed the impact that offering
a pacifier or other nonlactating nipple to a neonate
has on breastfeeding. This subject area would be an
interesting one to explore. Another recommendation
is to conduct more studies with clinically validated
pain assessment tools and larger sample sizes and
include VLBW, ill neonates. This review provides
implications for clinical practice in that sucrose and
NNS can be considered for standard care policy for
procedural pain in NICUs with the confidence that
it is safe and effective. Sucrose has been widely stud-
ied and found to produce a calming effect and reduce
procedural pain. Sucking is well known to be calm-
ing in neonates, but the calming effect is often lost
once the stimulus is removed. The combination of
sucrose and NNS increases the calming effect in neo-
nates during procedural pain. Neonates, both full-
term and preterm, undergo multiple painful proce-
dures during a hospital stay, whether it be a routine
For more than 69 additional articles related to neonatal topics,
go to NursingCenter.com/CE.
Advances in Neonatal Care • Vol. 13, No. 1
Copyright © 2013 National Association of Neonatal Nurses. Unauthorized reproduction of this article is prohibited.
ANC200347.indd 19
Sucrose and NNS for Procedural Pain in Neonates 19
healthy newborn hospital stay or an extended NICU
stay.2,5,6 Studies have demonstrated that neonates
feel pain as older children and adults do, and pain in
the neonate can lead to both short- and long-term
effects physically and developmentally.1,5,10 Because
of this, it is imperative to provide relief to these neo-
nates during painful procedures. The direct care
nurse should use this substantial evidence in clinical
practice. They should inquire as to whether or not
there is a policy in place on their unit and if there is
not one, they should work to create a policy. Sucrose
in combination with NNS is a safe and effective non-
pharmacologic means of relieving pain in neonates
and should be used regularly in clinical practice for
painful procedures.
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