"Joe" a well respected RN with many years of experience, worked in the intensive care unit. One afternoon a patient was brought to the unit immediately post heart surgery. Joe assumed his care, and began his assessment. Shortly after the patient's arrival, the surgeon came in to see that patient.
The surgeon decided that he needed to replace a blocked central line, although the patient did have two patent peripheral IVs. Joe assisted the surgeon with the line placement, then called for radiology to come up and confirm line placement, as per protocol. Just as Joe heard the radiology tech coming, the patient developed asystole. Joe and the surgeon instituted ACLS protocol. When the surgeon called for a medication to be pushed, Joe went to push it via the patent peripheral IV, as placement of the central line had not been confirmed. The surgeon yelled 'No! In the central line! Push it in the central line!' Joe responded, 'The central line placement has not been confirmed, so it has to go through the peripheral." At this point, the surgeon yelled, "I want it through the central line, and you have to do what I say, because I'm the physician!" Joe yelled back that he was not going to risk his license just because a physician refused to follow protocol. He told the surgeon that he would push it through the peripheral line. The surgeon was livid, but made no attempt to push the med himself, so Joe pushed it through the peripheral line. The patient was then revived.
Joe and the surgeon continued to argue after the patient was resuscitated, to the point where other staff feared a fist fight would ensue. The house manager, an RN, was called in. Joe explained the situation to her. The surgeon said "I told him he was a nurse and he had to do what I told him to do. He's not going to lose his license or get fired as long as he does what I tell him to do. But he won't listen."
The house manager responded. "Well, the hospital policy does say that central lines cannot be used until placement has been confirmed by radiology." The surgeon went berserk, yelling at everyone. The house manager then said "well, if you want, we can change that policy so if a physician says it's ok, the line can be used without confirmation."
What do you think of the house manager's response to the situation?
What, if anything, do you think Joe should have done differently?
How would you have responded?
What do you suggest should be done about this proposed change in the policy?
Contents lists available at ScienceDirect
International Journal of Nursing Studies
journal homepage: www.elsevier.com/locate/ijns
Effect of non-nutritive sucking and sucrose alone and in combination for
repeated procedural pain in preterm infants: A randomized controlled trial
Haixia Gaoa,⁎, Mei Lib, Honglian Gaoc, Guihua Xua, Fang Lib, Jing Zhoub, Yunsu Zoub,
Honghua Jiangb
a School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China
b Children’s Hospital of Nanjing Medical U ...
Joe a well respected RN with many years of experience, worked in.docx
1. "Joe" a well respected RN with many years of experience,
worked in the intensive care unit. One afternoon a patient was
brought to the unit immediately post heart surgery. Joe assumed
his care, and began his assessment. Shortly after the patient's
arrival, the surgeon came in to see that patient.
The surgeon decided that he needed to replace a blocked central
line, although the patient did have two patent peripheral IVs.
Joe assisted the surgeon with the line placement, then called for
radiology to come up and confirm line placement, as per
protocol. Just as Joe heard the radiology tech coming, the
patient developed asystole. Joe and the surgeon instituted ACLS
protocol. When the surgeon called for a medication to be
pushed, Joe went to push it via the patent peripheral IV, as
placement of the central line had not been confirmed. The
surgeon yelled 'No! In the central line! Push it in the central
line!' Joe responded, 'The central line placement has not been
confirmed, so it has to go through the peripheral." At this point,
the surgeon yelled, "I want it through the central line, and you
have to do what I say, because I'm the physician!" Joe yelled
back that he was not going to risk his license just because a
physician refused to follow protocol. He told the surgeon that
he would push it through the peripheral line. The surgeon was
livid, but made no attempt to push the med himself, so Joe
pushed it through the peripheral line. The patient was then
revived.
Joe and the surgeon continued to argue after the patient was
resuscitated, to the point where other staff feared a fist fight
would ensue. The house manager, an RN, was called in. Joe
explained the situation to her. The surgeon said "I told him he
was a nurse and he had to do what I told him to do. He's not
going to lose his license or get fired as long as he does what I
tell him to do. But he won't listen."
2. The house manager responded. "Well, the hospital policy does
say that central lines cannot be used until placement has been
confirmed by radiology." The surgeon went berserk, yelling at
everyone. The house manager then said "well, if you want, we
can change that policy so if a physician says it's ok, the line can
be used without confirmation."
What do you think of the house manager's response to the
situation?
What, if anything, do you think Joe should have done
differently?
How would you have responded?
What do you suggest should be done about this proposed change
in the policy?
Contents lists available at ScienceDirect
International Journal of Nursing Studies
journal homepage: www.elsevier.com/locate/ijns
Effect of non-nutritive sucking and sucrose alone and in
combination for
repeated procedural pain in preterm infants: A randomized
controlled trial
Haixia Gaoa,⁎, Mei Lib, Honglian Gaoc, Guihua Xua, Fang Lib,
Jing Zhoub, Yunsu Zoub,
Honghua Jiangb
3. a School of Nursing, Nanjing University of Chinese Medicine,
Nanjing, China
b Children’s Hospital of Nanjing Medical University, China
c Binzhou Medical University Hospital, Binzhou, China
A R T I C L E I N F O
Keywords:
Preterm infants
Pain
Analgesia
Sucrose
Non-nutritive sucking
A B S T R A C T
Background: Sucrose combined with non-nutritive sucking
provided better pain relief than sucrose or non-nu-
tritive sucking alone in a single painful procedure. However,
whether the combination of non-nutritive sucking
with sucrose could obtain a significant difference in analgesic
effect of the repeated procedural pain than any
single intervention has not been established.
Objective: To compare the effect of non-nutritive sucking and
sucrose alone and in combination of repeated
procedural pain in preterm infants.
Design: Randomized controlled trial.
Setting: A level III neonatal intensive care unit of a university
hospital in China.
Method: Preterm infants born before 37 weeks of gestation were
randomly assigned to four groups: routine care
group (routine comfort through gentle touch when infants cried;
n = 21), non-nutritive sucking group (n = 22),
sucrose group (0.2 ml/kg of 20%; n = 21), sucrose (0.2 ml/kg of
20%) plus non-nutritive sucking group
4. (n = 22). Each preterm infant received three nonconsecutive
routine heel sticks. Each heel stick included three
phases: baseline (the last 1 min of the 30 min without stimuli),
blood collection, recovery (1 min after blood
collection). Three phases of 3 heel stick procedures were
videotaped. Premature infant pain profile (PIPP) score,
heart rate, oxygen saturation and percentage of crying time were
assessed by five independent evaluators who
were blinded to the purpose of the study at different phases
across three heel sticks. Data were analyzed by
analysis of variance, with repeated measures at different
evaluation phases of heel stick.
Results: 86 preterm infants completed the protocol. During the
blood collection and recovery phases, combi-
nation group, had lower PIPP score (4.4 ± 1.5; 3.0 ± 0.8), lower
heart rate (138.6 ± 7.9; 137.4 ± 4.7),
higher oxygen saturation (95.2 ± 1.6; 96.0 ± 1.2), and smaller
percentage of crying time (11.5 ± 8.6;
4.6 ± 3.4), compared with the group has given non-nutritive
sucking (9.3 ± 1.3, 6.8 ± 1.4; 154.2 ± 9.0,
148.0 ± 9.3; 92.9 ± 2.4, 94.1 ± 1.0; 44.2 ± 9.6, 31.2 ± 10.5;
respectively) or sucrose (10.1 ± 2.0,
7.4 ± 1.6; 151.6 ± 9.6, 147.9 ± 6.9; 93.5 ± 1.7, 94.5 ± 1.2; 53.8
± 16.7, 35.2 ± 13.9; respectively) or
routine care (13.3 ± 1.6, 10.6 ± 1.9; 156.8 ± 7.2, 151.7 ± 7.9;
92.9 ± 2.1, 93.8 ± 1.6; 80.6 ± 7.6,
68.2 ± 9.9; respectively). Both non-nutritive sucking and
sucrose were more effective in reducing preterm
infants’ PIPP score and percentage of crying time than routine
care. There was no difference in PIPP score, heart
rate, oxygen saturation and percentage of crying time between
the non-nutritive sucking and sucrose groups.
Conclusion: The combination of non-nutritive sucking with
sucrose provided better pain relief during repeated
painful procedures than when non-nutritive sucking or sucrose
was used alone. The effect of non-nutritive
6. https://doi.org/10.1016/j.ijnurstu.2018.04.006
mailto:[email protected]
https://doi.org/10.1016/j.ijnurstu.2018.04.006
http://crossmark.crossref.org/dialog/?doi=10.1016/j.ijnurstu.201
8.04.006&domain=pdf
• The use of sucrose alone or combined with non-nutritive
sucking has
been the most frequently studied non-pharmacological
intervention
method for single procedural pain. However, there have been no
studies comparing the effect of sucrose and non-nutritive
sucking
alone and in combination with repeated procedural pain for
preterm
infants.
What this paper adds
• The combination of sucrose and non-nutritive sucking shows
better
efficacy for repeated procedural pain than their single use in
pre-
term infants.
• The effect of non-nutritive sucking was similar to that of
sucrose on
repeated procedural pain.
• When both sucrose and non-nutritive sucking can be provided
in a
unit, the combination of them can be recommended as an
analgesic
alternative for repeated pain exposure in preterm infants.
7. 1. Introduction
Preterm birth is a significant global health problem. Survival
rates
for preterm infants have increased markedly in recent decades
due to
significant advances in neonatal intensive care. However,
preterm in-
fants are exposed to various painful stimuli to guarantee their
survival
during their stay in the neonatal intensive care unit (Chen et al.,
2012;
Cruz et al., 2016; Jeong et al., 2014). Greater exposure to
neonatal
pain-related stress has been found to be associated with poorer
long-
term neurodevelopmental outcomes (Brummelte et al., 2012;
Doesburg
et al., 2013; Lax et al., 2013; Skranes et al., 2012; Smith et al.,
2011;
Vinall et al., 2013; Nuseir et al., 2015). Therefore,
pharmacological or
non-pharmacological pain management must be required for
preterm
infants in current neonatal practice.
Opioid analgesia is now widely used in preterm neonates. It is
no-
teworthy that several recent studies have demonstrated repeated
ex-
posure of preterm infants to opioid may have a detrimental
effect on
child neurodevelopmental outcomes (Nuseir et al., 2015). For
example,
the result from Nunes et al. study showed that repeated
morphine ex-
8. posure during early life could have intermediate and long-term
adverse
effects on the nociceptive responses, which included thermal
hyper-
algesia and mechanical allodynia (Nunes et al., 2017). Kocek et
al.
observed decreasing cognitive scores at 20 months corrected age
in
extremely low birth weight infants who had cumulative opioid
ex-
posure while in the neonatal intensive care unit (Kocek et al.,
2016).
Furthermore, Ranger et al. reported that higher cumulative
doses of
neonatal morphine were related with higher internalizing
behaviours at
school age (Ranger et al., 2014). Thus, the adverse effects of
opioid
analgesic are not negligible. It is very important to better
understand
the potential risks and benefits of repeated opioid exposure in
preterm
infants.
In contrast to pharmacological pain management, non-
pharmaco-
logical pain management may have lower risk and greater ease
of use
for preterm infants. Sucrose and non-nutritive sucking are the
most
frequently studied non-pharmacological methods for reducing a
single
procedural pain in preterm infants, and have been recommended
by
national and international guidelines to alleviate procedural
pain.
9. Furthermore, recent systematic reviews have addressed sucrose
and
non-nutritive sucking as effective interventions to provide
analgesia
and comfort for infants during painful procedures (Pillai Riddell
et al.,
2015; Stevens et al., 2016). However, the evidence regarding
the effi-
cacy and safety of repeated sucrose alone or combined with
other non-
pharmacological interventions across repeated procedural pain
for
neonates was limited (Gao et al., 2016). What’s more, there
have been
no studies examining whether the combined intervention of
sucrose and
non-nutritive sucking could obtain a significant difference in
analgesic
effect on repeated procedural pain compared to any single
intervention
for preterm infants, although several studies have reported that
sucrose
combined with non-nutritive sucking provided better pain relief
than
sucrose or non-nutritive sucking alone in a single painful
procedure (Liu
et al., 2017; Naughton, 2013; Thakkar et al., 2016). It is a
remarkable
fact that preterm newborns could learn and react to painful
experiences
in the neonatal intensive care unit (Goubet et al., 2001), and the
re-
peated exposure to painful experiences may reduce the pain
threshold
and provoke hyperalgesia (Gibbins et al., 2008; Grunau, 2002).
10. Thus, it
is vital to determine if the effects of the combination of sucrose
and
non-nutritive sucking are better than their single-use on
repeated pro-
cedural pain for preterm infants. In addition, animal studies
have
shown that continuous consumption of sucrose can induce some
be-
havioral and physiological responses similar to those elicited by
drugs
of abuse like cocaine or amphetamine (Avena et al., 2008).
Therefore,
the safety of repeated administration of sucrose or non-nutritive
sucking or their combination during painful procedures for
preterm
infants needs to be examined.
Hence, the purpose of this study was to compare the efficacy
and
safety of sucrose, non-nutritive sucking, and in combination
with re-
peated procedural pain in preterm infants. We hypothesized
that: (1)
Combined intervention of sucrose and non-nutritive sucking
could be
more effective than any single intervention across repeated
procedural
pain; (2) It is safe for preterm infants to use non-nutritive
sucking or
sucrose alone or their combination repeatedly across repeated
painful
procedures.
2. Methods
11. 2.1. Design
This randomized controlled trial evaluated and compared the ef-
fectiveness of sucrose and non-nutritive sucking alone and in
combi-
nation with repeated procedural pain across three
nonconsecutive
routine heel sticks in preterm infants. Preterm infants were
randomly
allocated before the heel stick by a research nurse using a
random
computer-generated table to one of the four groups: routine care
group,
non-nutritive sucking group, oral sucrose group, combined oral
sucrose
and non-nutritive sucking group.
2.2. Setting and sample
Preterm infants were recruited by convenience sampling from a
level III neonatal intensive care unit (NICU) of a university
hospital in
China from August 2015 to February 2016. Infants were
included if
they met the following inclusion criteria: (1) Singleton born
before 37
weeks of gestation, (2) Cared for in an incubator, (3)
Anticipated re-
ceiving at least three routine heel sticks for capillary blood
sampling
within two weeks after birth, (4) Hospitalized for the first time,
(5)
Non-nutritive sucking rate at a minimum of 30 times/min (Blass
and
Watt, 1999), and (6) Not scheduled to receive sedatives, muscle
re-
12. laxants, or analgesic drugs 24 h before a study session. Infants
were
excluded by these criteria: (1) Apgar Score of less than five at
five
minutes, (2) Required mechanical ventilation, (3) Suffered from
a
neurologic disorder, (4) Had congenital anomalies, (5)
Undergone
surgery, (6) Born to substance-abusing mother, (7) Had
hyperglycemia,
and (8) Nothing by mouth status for any reason.
To identify unforeseen problems and calculate the sample size,
we
conducted a pilot study. Our pilot study showed the average
Preterm
Infant Pain Profile (PIPP) score in 10 preterm infants during
heel sticks
were 11.7 (SD = ± 5.5) in routine care group, 10.8 (SD = ± 4.2)
in
non-nutritive sucking group, 9.0 (SD = ± 3.6) in oral sucrose
group,
7.3 (SD = ± 2.0) in combined oral sucrose and non-nutritive
sucking
group. To detect a significant difference in PIPP score among
the four
groups, considering a power of 0.90, alpha of 0.05, and a 10%
attrition
rate, a sample size of 22 was required in each group.
H. Gao et al. International Journal of Nursing Studies 83 (2018)
25–33
26
13. 2.3. Conditions in the four groups
All preterm infants, wearing only a diaper, were placed prone or
in a
side-lying position in the incubator and remained undisturbed
for
30 min before the heel stick procedure. The assigned treatment
condi-
tion was administered by one researcher (the first author).
2.3.1. The condition in the routine care group
The preterm infant received only routine comfort through gentle
touch when he cried after the heel stick procedure. The
effectiveness of
gentle touch as analgesia has been established in controlled
clinical
trials (Bahman Bijari et al., 2012; Herrington and Chiodo,
2014). Thus,
for ethical reasons, preterm infants in the routine care group
were given
gentle touch to alleviate procedural pain if they were crying.
2.3.2. The condition in the non-nutritive sucking group
The preterm infant was given a standard silicone newborn
pacifier
to stimulate sucking in 2 min before, and throughout the
recovery phase
of the heel stick.
2.3.3. The condition in the sucrose group
Sucrose 20% (0.2 ml/kg) was administrated to the preterm
infant’s
14. mouth by 1 ml syringe without the needle in 2 min before the
heel stick
procedure (Cignacco et al., 2012).
2.3.4. The condition in the combined oral sucrose and non-
nutritive sucking
group
Sucrose 20% (0.2 ml/kg) was administrated to the preterm
infant’s
mouth by 1 ml syringe without the needle in 2 min before the
heel stick
procedure (Cignacco et al., 2012), and then a standard silicone
new-
born pacifier was given to stimulate sucking until the recovery
phase of
the heel stick.
2.4. Measures
Outcome variables included preterm infants’ procedural pain,
phy-
siological response, behavioral response, and incidence of any
adverse
events.
2.4.1. Measurement of procedural pain
The preterm infants’ procedural pain was measured by the
Premature Infant Pain Profile (PIPP) scale. The PIPP scale is a
validated
seven-indicator scale for the assessment of procedural pain in
pre-
mature and term infants (Stevens et al., 1996). It measures pain
ac-
cording to two contextual indicators (gestational age and
15. behavioral
state), two physiological indicators (heart rate and oxygen
saturation),
and three behavioral indicators (brow bulge, eye squeeze, and
nasola-
bial furrow). Each indicator is numerically scaled and scored on
a 4-
point scale (0, 1, 2, 3), the total scores obtained for the seven
indicators
range from 0 to 21. Higher total scores indicate greater pain
response.
PIPP score < 6 means no pain, PIPP score ≥6 indicates pain,
PIPP
scores ≥12 signals moderate to severe pain. Validity and
reliability of
the PIPP instrument in infants at various gestational ages has
previously
been determined. For translation of PIPP scale from English
into Chi-
nese, the standard forward-backward procedure was applied.
Transla-
tion of the PIPP scale (English to Chinese) was independently
per-
formed by two professional translators, and then the temporary
version
was provided. The temporary version of the PIPP scale was
backward
translated into English by a native English translator who was
blinded
to the original instrument and not previously involved in the
study. The
back-translator and the expert committee evaluated the back-
translated
version, then the final version of the PIPP scale was provided.
Physiological indicators were continuously monitored by a
16. pulse
oximeter set on the preterm infant’s foot and videotaped by one
digital
camera (Canon sx30is). Behavioral indicators and behavioral
state in-
dicator were continuously videotaped by another digital camera
(Canon
sx30is) which was in close up focus on preterm infants’ face
and al-
lowed for high-quality facial images. The two digital cameras
(Canon
sx30is) were used synchronously by the research assistant. The
beha-
vioral state indicator was evaluated using Prechtl's categories of
quiet
sleep or quiet awake or active sleep or active awake (Prechtl,
1974;
Prechtl and Beintema, 1977). Gestational age was determined
ac-
cording to the electronic medical record. PIPP score was
measured by
two trained evaluators (the second and third author) who were
una-
ware of the purpose of the study during the blood collection
phase and
recovery phase of each heel stick procedure. In order to ensure
accep-
table inter-rater agreement, the two evaluators respectively
assessed
PIPP score for each preterm infant at the blood collection phase
of the
first heel stick, the inter-rater reliability among evaluators was
97%.
Intra-rater reliability was checked every three months,
remaining more
17. than 90%.
2.4.2. Measurement of physiological response
The preterm infant’s physiological response to procedural pain
was
assessed by the change in heart rate and oxygen saturation
throughout
repeated heel sticks. Oxygen saturation and heart rate were con-
tinuously monitored by a pulse oximeter set on the preterm
infant’s
foot, were manually recorded every 30 s by a nurse student, and
then
were used to calculate the mean heart rate and oxygen
saturation across
the baseline, blood collection and recovery phases of each heel
stick
procedure.
2.4.3. Measurement of behavioral response
The preterm infant’s behavioral response to procedural pain was
measured by the percentage of crying time respectively in the
blood
collection phase and recovery phase. Crying was defined as
audible
vocalization that lasted five seconds or more (Ludington-Hoe et
al.,
2005). Preterm infants’ voices were videotaped by a digital
audio re-
corder (MODEL F97), and then two assessors calculated the
percentage
of crying time through playing the tapes. To examine the inter-
rater
agreement, the two assessors, respectively calculated the
percentage of
18. crying time at the blood collection phase of the first heel stick,
and the
inter-rater reliability between the assessors was 98%. Intra-rater
relia-
bility was checked every three months, remaining more than
90%.
2.4.4. Measurement of incidence of adverse events
The safety of different interventions (non-nutritive sucking,
sucrose,
and combined use of them) was assessed by the incidence of
adverse
events during the study period. The adverse events included: (1)
Choking, coughing, vomiting, abdominal distension, oral
infection,
necrotizing enterocolitis; (2) Sustained tachycardia (heart rate >
200
beats/min), bradycardia (heart rate < 80 beats/min), tachypnea
(re-
spiratory rate > 80 beats/min), dyspnea (respiratory rate < 20
beats/
min), or oxygen desaturation < 80% for > 15 s; (3)
Hyperglycemia.
The adverse events were monitored and recorded by two trained
re-
search nurses who were blind to the purpose of the study. A
safety
committee was established prior to study commencement. If
severe
adverse event such as choking or need for immediate medical
inter-
vention (e.g., intubation or resuscitation) following the
administration
of non-nutritive sucking, sucrose, or their combination
occurred, the
19. trial would be stopped by the safety committee.
2.5. Procedures
The study protocol (Fig. 1) and consent forms were approved by
the
institutional review board of the participating centre (approval
number:
201507001-1). One research assistant screened admission log
every
other day in the neonatal intensive care unit, and finalized
potential
eligible infants, and informed the preterm infant’s parent of the
purpose
of the study, and obtained parental oral consent. Participating
preterm
infants were randomly assigned to the routine care group, non-
nutritive
sucking group, oral sucrose group, or combined intervention
group. The
H. Gao et al. International Journal of Nursing Studies 83 (2018)
25–33
27
research assistant collected preterm infant’s characteristics, set
pulse
oximeter on the preterm infant’s foot at about 5 min before the
heel-
stick procedure. One researcher administered the intervention
ac-
cording to the assigned condition, and then the experienced
laboratory
20. employee performed heel stick in a standardized manner. One
research
nurse videotaped preterm infant’s physiological indicators in 15
s be-
fore and 30 s after the heel stick, and in 15 s before and 30 s
after the
end of the heel stick, and videotaped preterm infant’s facial
actions in
30 s after the heel stick and 30 s after the end of the heel stick.
The other
research nurse videotaped preterm infants’ voices occurring in
the heel
stick procedure by a digital audio recorder. Because the timing
of blood
sampling was determined by clinical needs, there were no fixed
time
points for data collection. Most heel-stick events took place in
the
morning and the intervals of them ranged from 3 to 48 h.
Each heel stick included three phases: (1) Baseline: 1 min of
baseline
was collected at the end of the 30 min without stimuli. (2)
Blood col-
lection: includes locating the site, disinfecting, sticking,
squeezing,
applying adhesive bandage to the site for hemostasis, which
lasted
about 60 s according to our previous observation. (3) Recovery:
one
min after blood collection. The mean heart rate and oxygen
saturation
during three phases of each heel stick, which displays in a pulse
oxi-
meter, were collected by a nurse student (see Section 2.4.2).
Preterm
21. infants’ PIPP score and percentage of crying time across the
whole heel
stick were evaluated by four assessors (see Sections 2.4.1;
2.4.3). All
personnel was trained separately by the first author.
Study fidelity was established by the first author having
separate
weekly meetings with the investigators, research assistant,
nursing
student, and laboratory employees.
2.6. Data analysis
SPSS version 21.0 software package was used to conduct all the
descriptive and comparative statistical analysis. Data were
presented as
means and standard deviations for continuous variables and
frequencies
for categorical variables. Preterm infant’s characteristics such
as birth
weight were evaluated for significant differences between the
four
groups by one-way ANOVA test or Kruskal–Wallis analysis
when the
assumption of normality test could not be found. For preterm
infant’s
characteristics such as sex and the incidence of adverse events,
Chi-
square test was used to determine whether there was significant
dif-
ference between groups. For comparisons among the different
phases,
measurement parameters (PIPP score, heart rate, oxygen
saturation,
22. and the percentage of crying time) through the repeated heel
sticks
were averaged separately. Repeated measurement analysis of
variance
was performed to analyze both between- and within-groups
difference
in three phases, followed by the Bonferroni post-hoc test. For
all com-
parisons, a p- value of less than 0.05 was considered
statistically sig-
nificant.
3. Results
There were 137 preterm infants were screened during the data
collection period. 103 were eligible for the criteria and were ap-
proached, and 91 agreed to participate. The reasons for refusals
in-
cluded parents: did not want their infants to be videotaped due
to their
small size (n = 7), refused anything extra done to their infants
(n = 3),
were not interested (n = 2). Five infants dropped out of the
study be-
cause they were discharged from the unit prior to the required
heel
stick (Fig. 2). Preterm infant’s characteristics did not vary
significantly
between infants whose parents declined to participate or
dropped out of
the study (n = 17) and those who completed the study protocol
(n = 86).
3.1. Preterm infant characteristics
The characteristics of preterm infants completed the study
23. protocol
are shown in Table 1. The sample included 86 preterm infants
with a
mean gestational age of 31.7 ± 0.9 weeks. The majority was
male
(60%) and born by cesarean delivery (71%). The preterm
infants’ mean
birth weight was 1732.0 ± 267.9 g, mean Apgar score at 5 min
was
8.8 ± 0.7, and they had 15.7 ± 2.4 previous invasive procedures.
No
significant differences were noted among the four groups with
regard to
the preterm infants’ characteristics.
3.2. Comparison of pain measurement parameters during the
three repeated
heel sticks between groups
3.2.1. Between-group differences in pain measurement
parameters during
the repeated three heel sticks
We compared the effectiveness of routine care, non-nutritive
sucking, sucrose and their combination in reducing procedural
pain
during repeated heel sticks. The results of repeated
measurement
Fig. 1. The study protocol.
H. Gao et al. International Journal of Nursing Studies 83 (2018)
25–33
28
24. analysis of variance between groups revealed significant
interactions of
all the pain measurement parameters except PIPP score between
treatment conditions and evaluation phases (PIPP score: F =
1.995,
p = 0.121; heart rate: F = 11.509, p < 0.0001; oxygen saturation:
F = 2.886, p = 0.016; percentage of crying time: F = 72.517,
p < 0.0001). Moreover, there was a significant main effect of
the
treatment groups for all the pain measurement parameters (PIPP
score:
F = 168.360, p < 0.0001; heart rate: F = 16.983, p < 0.0001;
oxygen
saturation: F = 10.165, p < 0.0001; percentage of crying time:
F = 275.310, p < 0.0001). Post hoc analyses were performed to
compare the treatment conditions with each other (Table 2). In
the
baseline phase, there was no significant difference in heart rate,
oxygen
saturation and percentage of crying time respectively between
groups
with each other. Thus, all pain parameters during the blood
collection
phase and the recovery phase were comparable between groups.
During
the blood collection phase and recovery phase, regarding PIPP
score,
the combination group was significantly lower than the other
three
groups, both the sucrose group and non-nutritive group were
lower
than the routine care group. Regarding heart rate and oxygen
satura-
tion, the combination group had achieved a significant
25. improvement
compared with the other three groups, while there were no
significant
difference among the routine care group, sucrose group and
non-nu-
tritive sucking group. Regarding the percentage of crying, the
combi-
nation group was significantly smallest, the routine care group
was
significantly biggest, the non-nutritive sucking group was
significantly
similar to the sucrose group.
3.2.2. Within-group differences in pain measurement parameters
during the
repeated three heel sticks
PIPP score, heart rate, oxygen saturation and percentage of
crying
time showed similar patterns in the four treatment groups,
which
changing significantly followed by the blood collection phase
and re-
covering afterwards (Table 3). In the blood collection phase, the
mean
PIPP scores at heel stick 1, 2, and 3 for the four treatment
groups were
as follows: 13.2 ± 2.1, 13.1 ± 1.7, 13.4 ± 2.6 respectively in the
control group, 9.9 ± 2.4, 8.5 ± 2.7, 9.5 ± 2.6 respectively in the
non-nutritive sucking group, 11.1 ± 2.1, 10.1 ± 3.9, 8.9 ± 4.0 re-
spectively in the sucrose group, 4.2 ± 2.1, 4.8 ± 2.9, 4.4 ± 2.0
re-
spectively in the combination group. In the recovery phase, the
mean
PIPP score at heel stick 1, 2, and 3 for the four treatment groups
26. were as
follows: 10.5 ± 2.5, 10.7 ± 1.9, 10.5 ± 2.5 respectively in the
con-
trol group, 7.6 ± 2.2, 6.0 ± 2.6, 6.9 ± 2.6 respectively in the
non-
nutritive sucking group, 7.9 ± 1.8, 7.3 ± 3.3, 7.1 ± 2.7
respectively
in the sucrose group, 3.1 ± 2.0, 3.1 ± 1.7, 2.8 ± 1.0 respectively
in
the combination group. The dada above showed that preterm
infants in
the combination group didn’t feel pain at each heel stick,
infants in the
sucrose and non-nutritive sucking group felt mild pain, while
infants in
the control group felt moderate to severe pain.
Within-group comparison showed that significant differences in
heart rate and oxygen saturation between the baseline phase and
Assessed for eligibility (n=137)
Excluded (n =46)
Mee ng exclusion criteria (n =34)
Refused to par cipate (n = 12)
n =91
Randomly allocated
Allocated to rou ne care
group (n=23)
In all three nonconsecu ve
heel s cks, infants received
allocated incubator
condi on
27. Heel s ck 1 (n=23)
Heel s ck 2 (n=23)
Heel s ck 3 (n=21) :
2 infants discharged prior to
the third heel s ck
Allocated to nonnutri ve
sucking group (n=23)
In all three nonconsecu ve
heel s cks, infants received
allocated nonnutri ve
sucking
Heel s ck 1 (n=23)
Heel s ck 2 (n=23)
Heel s ck 3 (n=22) :
1 infant discharged prior to
the third heel s ck
Allocated to sucrose group
(n=23)
In all three nonconsecu ve
heel s cks, infants received
allocated oral sucrose
Heel s ck 1 (n=23)
Heel s ck 2 (n=23)
Heel s ck 3 (n=21):
2 infants discharged prior
to third heel s ck
Allocated to combina on
group (n=22)
In all three nonconsecu ve
heel s cks, infants received
28. allocated combined
treatment
Heel s ck 1 (n=22)
Heel s ck 2 (n=22)
Heel s ck 3 (n=22)
Analyzed
Repeated three heel s cks
(n=21)
Analyzed
Repeated three heel s cks
(n=22)
Analyzed
Repeated three heel s cks
(n=21)
Analyzed
Repeated three heel s cks
(n=22)
Fig. 2. Flow diagram of the recruitment and randomization
process.
H. Gao et al. International Journal of Nursing Studies 83 (2018)
25–33
29
29. recovery phase approached for all groups except the
combination
group. For the routine care group, sucrose group, non-nutritive
sucking
group, heart rate remained significantly quicker in recovery
phase than
in baseline phase, oxygen saturation remained significantly
lower in
recovery phase than in baseline phase. However, both heart rate
and
oxygen saturation in the combination group remained steady
across all
phases. In addition, compared to the other three group infants,
com-
bination group infants’ mean percentage of crying time in the
recovery
phase was near to the baseline phase percentage, although
significant
differences occurred in all groups between the baseline phase
and the
recovery phase.
3.3. Comparison of incidence of adverse events in the study
period between
groups
The incidence of adverse events in the study period was as
follows:
three preterm infants vomited (1 in the combination group, 1 in
the
routine care group, 1 in the non-nutritive sucking group); two
preterm
infants had abdominal distension (1 in the combination group, 1
in the
routine care group). The Chi-square test exhibited that there
were no
30. statistically significant differences between groups in the
incidence of
adverse events (vomit: χ2 = 1.006, p = 0.800; abdominal
distension:
χ2 = 2.050, p = 0.562).
Table 1
Comparisons of characteristics of preterm infants between
groups.
Variable Routine care group Nonnutritive sucking group
Sucrose group Combination group P value
Gestational age, week
30–32a 21 16 17 18
33–34a 0 6 4 4 0.102
Gender
Malea 13 15 10 14
Femalea 8 7 11 8 0.550
Method of delivery
Vaginal deliverya 5 9 6 5
Cesarean deliverya 16 13 15 17 0.530
Birth weight, gb 1682.7 ± 200.2 1767.3 ± 302.7 1780.8 ± 304.6
1697.1 ± 254.7 0.547
Gestational age at birth, weekb 31.3 ± 0.6 31.9 ± 1.1 31.7 ± 0.9
32.0 ± 0.8 0.068
5 min Apgar scoreb 8.7 ± 0.6 8.8 ± 0.6 8.9 ± 0.7 8.8 ± 0.8 0.846
Postnatal days
Heel stick 1b 3.2 ± 0.6 3.5 ± 0.6 3.4 ± 0.6 3.2 ± 0.7 0.262
Heel stick 2b 5.4 ± 0.6 5.4 ± 0.7 5.3 ± 0.6 5.6 ± 0.7 0.580
Heel stick 3b 9.5 ± 1.0 8.2 ± 2.0 8.5 ± 1.4 9.0 ± 2.9 0.179
31. Previous invasive proceduresb 15.7 ± 2.2 14.9 ± 2.9 16.1 ± 2.0
16.0 ± 2.3 0.359
Duration of blood collection phase, seconds
Heel stick 1b 61.9 ± 12.5 61.5 ± 9.3 59.8 ± 9.7 57.7 ± 9.9 0.544
Heel stick 2b 65.5 ± 9.6 62.7 ± 12.8 66.9 ± 18.2 61.6 ± 13.7
0.573
Heel stick 3b 64.1 ± 9.2 58.7 ± 11.1 63.2 ± 9.0 59.1 ± 13.2
0.240
Behavioral state score at baseline phase
Heel stick 1b 0.9 ± 0.7 0.8 ± 0.7 0.8 ± 0.7 0.9 ± 0.9 0.893
Heel stick 2b 1.1 ± 0.7 0.7 ± 0.6 0.8 ± 0.7 0.9 ± 0.6 0.216
Heel stick 3b 0.4 ± 0.5 0.4 ± 0.5 0.4 ± 0.5 0.3 ± 0.5 0.938
a n.
b Mean (standard deviation).
Table 2
Between-group comparison of pain measurement parameters
during the repeated three heel sticks.
RC group −NS group RC group −S group RC group −C group
NS group-S group NS group- C group S group- C group
PIPP score
Blood collectiona P < 0.0001 P < 0.0001 P < 0.0001 0.694 P <
0.0001 P < 0.0001
Recoverya P < 0.0001 P < 0.0001 P < 0.0001 1.000 P < 0.0001
P < 0.0001
Heat rate (beats/min)
Baselinea 0.203 1.000 1.000 0.283 1.000 1.000
Blood collectiona 1.000 0.305 P < 0.0001 1.000 P < 0.0001 P <
0.0001
Recoverya 0.621 0.610 P < 0.0001 1.000 P < 0.0001 P < 0.0001
32. Oxygen saturation (%)
Baselinea 1.000 1.000 1.000 1.000 1.000 1.000
Blood collectiona 1.000 1.000 0.002 1.000 0.002 0.035
Recoverya 1.000 0.602 P < 0.0001 1.000 P < 0.0001 0.001
Percentage of crying time (%)
Baselinea – – – – – –
Blood collectiona P < 0.0001 P < 0.0001 P < 0.0001 0.035 P <
0.0001 P < 0.0001
Recoverya P < 0.0001 P < 0.0001 P < 0.0001 1.000 P < 0.0001
P < 0.0001
Note: Data are listed as mean ± SD. PIPP: premature infant pain
profile; RC: Routine care; NS: Nonnutritive sucking; S:
Sucrose; C: Combination of nonnutritive
sucking and sucrose.
a Bonferroni correction for multiples comparisons.
H. Gao et al. International Journal of Nursing Studies 83 (2018)
25–33
30
4. Discussion
Studies have demonstrated that preterm infants could mount
both
physiological and behavioral responses to painful stimuli.
Repeated
painful stimuli in neonates may have short- and long-term con-
sequences on preterm infants physically and developmentally.
Therefore, it is imperative to provide relief for preterm infants
33. during
repeated painful procedures. Sucrose and non-nutritive sucking
have
been established for managing a single procedural pain.
However, to
our knowledge, this is the first study to examine the analgesic
effect of
non-nutritive sucking across repeated painful procedure, and to
de-
termine if the combined intervention of sucrose and non-
nutritive
sucking could obtain a significant difference in analgesic effect
on re-
peated procedural pain compared to any single intervention for
preterm
infants.
Our study represents that both sucrose and non-nutritive
sucking
could reduce preterm infants’ PIPP score and percentage of
crying time,
but neither of them could decrease preterm infants’
physiological re-
sponse during the repeated heel sticks, which is consistent with
the
previous studies (Table 2). Gaspardo et al. study found that
preterm
neonates in the sucrose group had significantly fewer facial
actions and
crying than the control group, but no statistical difference in the
per-
centage of neonates with a heart rate of > 160 beats/min
between
groups during repeated procedural pain (Gaspardo et al., 2008).
Cignacco et al. study, using the Bernese Pain Scale for
Neonates to
34. measure preterm infants’ pain response caused by five heel
sticks, re-
ported that sucrose was significantly more effective in relieving
re-
peated procedural pain than facilitated tucking (Cignacco et al.,
2012).
Boyer et al. study reported routine sucrose alone had no effect
on the
change in cortisol level and variability of heart rate which
resulted from
repeated procedural pain for preterm infants (Boyer et al.,
2004).
However, these previous studies differed from our study in the
fol-
lowing respects: (1) The method of evaluating procedural pain:
we
assessed preterm infants’ pain not only using Preterm Infant
Pain
Profile, but also using physiological and behavioral response,
whereas
other studies only used a pain scale, or physiological and
behavioral
response to measure preterm infants’ pain. (2) The
methodological as-
pect of study design: enough sample size used in our study,
while small
sample size in Gaspardo et al. study and moderate attrition rates
in
Boyer et al. study. These results suggest that clinicians in
Neonatal
Intensive Care Unit can provide non-nutritive sucking and
sucrose to
reduce preterm infants’ repeated procedural pain.
It is worthwhile to note that we could not find any study that
35. compared the analgesic effects of non-nutritive sucking in
preterm in-
fants to the analgesic effects of sucrose during repeated painful
proce-
dure. Our findings indicated that the analgesic effects of non-
nutritive
sucking in preterm infants was similar to that of sucrose during
re-
peated painful procedure. These study results provide an
alternative to
sucrose to relieve preterm infants’ repeated procedural pain.
However, we consider that either sucrose or non-nutritive
sucking is
not perfect analgesics, because both of them couldn’t reduce
preterm
infants’ physiological response following by repeated
procedural pain.
This present study demonstrated that the PIPP score, percentage
of
crying time, and magnitude of physiological response following
by re-
peated painful procedures were lowest in the combination of
sucrose
and non-nutritive sucking group, which indicated that sucrose
plus non-
nutritive sucking produced the most efficacious means of pain
reduc-
tion for repeated painful procedures. To date, only one study
has
evaluated the effect of sucrose combined with non-nutritive
sucking on
repeated procedural pain for preterm infants, which reported
PIPP
score was significantly lower in the sucrose with pacifier
intervention
36. group compared with the standard care group (Stevens et al.,
2005). Yet
in Stevens et al. study, the Premature Infant Pain Profile (PIPP)
scores
were not available on all preterm infants at all fixed data
collection
points due to some of the infants did not receive routine painful
pro-
cedure at each time point, which may affect the reliability of the
con-
clusion. The specific contribution of our study was that we
analyzed
exclusively sucrose in comparison to nonnutritive sucking, their
Table 3
Within-group comparison of pain measurement parameters
during the repeated three heel sticks.
Baselinea Blood collectiona Recoverya P (one-way RM
ANOVA)
PIPP score
Routine care group – 13.3 ± 1.6 10.6 ± 1.9 P < 0.0001
Nonnutritive sucking group – 9.3 ± 1.3 6.8 ± 1.4 P < 0.0001
Sucrose group – 10.1 ± 2.0 7.4 ± 1.6 P < 0.0001
Combination group – 4.4 ± 1.5 3.0 ± 0.8 P < 0.0001
Heat rate (beats/min)
Routine care group 133.1 ± 5.8b,c 156.8 ± 7.2 151.7 ± 7.9 P <
0.0001
Nonnutritive sucking group 137.0 ± 5.8b,d 154.2 ± 9.0 148.0 ±
9.3 P < 0.0001
Sucrose group 133.4 ± 5.6b,e 151.6 ± 9.6 147.9 ± 6.9 P <
0.0001
Combination group 134.7 ± 6.1b,f 138.6 ± 7.9 137.4 ± 4.7 0.080
37. Oxygen saturation (%)
Routine care group 95.7 ± 1.5b,c 92.9 ± 2.1 93.8 ± 1.6 P <
0.0001
Nonnutritive sucking group 95.8 ± 0.9b,d 92.9 ± 2.4 94.1 ± 1.0
P < 0.0001
Sucrose group 96.1 ± 1.5b,e 93.5 ± 1.7 94.5 ± 1.2 P < 0.0001
Combination group 96.1 ± 1.2b,f 95.2 ± 1.6 96.0 ± 1.2 0.024
Percentage of crying time (%)
Routine care group 0b,c 80.6 ± 7.6 68.2 ± 9.9 P < 0.0001
Nonnutritive sucking group 0b,d 44.2 ± 9.6 31.2 ± 10.5 P <
0.0001
Sucrose group 0b,e 53.8 ± 16.7 35.2 ± 13.9 P < 0.0001
Combination group 0b,g 11.5 ± 8.6 4.6 ± 3.4 P < 0.0001
Note: Data are listed as mean ± SD. PIPP: premature infant pain
profile.
a Mean (standard deviation).
b Bonferroni correction for multiples comparisons.
c Significant difference when compared with recovery–Routine
Care group (P < 0.05).
d Significant difference when compared with recovery–
Nonnutritive sucking group (P < 0.05).
e Significant difference when compared with recovery–Sucrose
group (P < 0.05).
f No significant difference when compared with recovery–
Combination group (P > 0.05).
g Significant difference when compared with recovery–
Combination group (P < 0.05).
H. Gao et al. International Journal of Nursing Studies 83 (2018)
25–33
31
38. combination and routine care, whereas Stevens et al. used
combined
sucrose plus pacifier in the same group in comparison with
pacifier plus
water and standard care.
Furthermore, our results found that preterm infants’ mean heart
rate
and oxygen saturation in the recovery phase had been back to
baseline
phase, and the percentage of crying time in the recovery phase
had
been near to baseline phase in the combination group (Table 3).
The
ability to recover quickly is a sign of ability to maintain
homeostasis, a
major task that the very preterm neonate must accomplish in
order to
grow and develop (Moore and Anderson, 2007). In summary,
the
combination of sucrose and non-nutritive sucking could have a
better
analgesic effect on repeated procedural pain than both methods
sepa-
rately. The plausible reason could be the multimodal stimulation
that
the preterm infant experiences when sucrose and non-nutritive
sucking
were administered together. These findings can guide nurses
and other
clinicians to combine sucrose and non-nutritive sucking to
minimize
preterm infants’ repeated procedural pain.
Establishing the safety of sucrose, non-nutritive sucking and
39. their
combination for repeated procedural pain might be the first
priority.
Our study demonstrated no significant difference in the
incidence of
adverse events between different groups. Thus, it indicates
sucrose,
non-nutritive sucking or their combination had no short-term
side ef-
fects on the health status of the preterm infants. Other authors
have
reported the similar results (Banga et al., 2016; Gaspardo et al.,
2008;
Stevens et al., 2005; Taddio et al., 2008).
The strengths of the present study included: (1) It was a
randomized
controlled trial with sufficient sample size. (2) Multiple
outcome vari-
ables (PIPP score, behavioral and physiological response) were
used to
evaluate the effect of sucrose, non-nutritive sucking, and in
combina-
tion on repeated procedural pain, which not only provided a
detailed
analysis over the entire sampling period, but also examined
their ef-
fectiveness on the overall changes in the summary scores. (3)
Videotaping, evaluating, offering treatment conditions were
performed
by different persons respectively, which enhanced the internal
validity
of the study results.
Despite its strengths, the study had some limitations: (1)
Preterm
40. infants enrolled in the study were stable and aged more than 30
weeks.
Thus, its results can not be generalized to the unstable and
extremely
preterm infants. (2) The study only focused on the analgesic
effects of
sucrose, non-nutritive sucking and their combination on
repeated heel
sticks, yet whether they could have the same analgesic effects
on other
repeated procedural pain as on repeated heel sticks had not been
de-
termined by the study. (3) The study examined the short-term
safety of
repeated sucrose, non-nutritive sucking and their combination
for
preterm infants, while the long-term impact of repeatedly
offering a
pacifier or sucrose or in combination during repeated procedural
pain
on preterm infants’ readiness for breastfeeding, weight gain and
even
neurobehavioral development had not been discussed. (4) The
Premature Infant Pain Profile especially its grimacing indicator
evalu-
ating procedure was impossible to be completely blind, because
non-
nutritive sucking had to be continued until 1 min after the
painful
procedure. (5) The control condition for our study was routine
care,
which might have led to unnecessary pain for preterm infants
assigned
to this condition, although this limitation was minimized by
offering
preterm infants in this condition gentle touch.
41. The implications for future research and practice may be as
follows:
Firstly, future studies should include the preterm infants with
gesta-
tional age less than 30 weeks and being medically unstable, and
then
examine and compare the efficacy and safety of sucrose, non-
nutritive
sucking, and their combination for repeated procedural pain in
them.
Secondly, researchers can further evaluate the effects of
sucrose, non-
nutritive sucking, and their combination on different types of
repeated
procedural pain except heel stick pain in preterm infants.
Thirdly,
further randomized controlled trials are needed to examine the
long-
term impact of repeatedly offering a pacifier or sucrose or their
com-
bination in repeated procedural pain on preterm infants during
their
stay in neonatal intensive care unit.
5. Conclusion
Both sucrose and non-nutritive sucking have a good analgesic
effect
for preterm infants on repeated procedural pain, but a
combination of
the two interventions shows better efficacy. Our results provide
evi-
dence supporting clinicians’ incorporation of the combined use
of su-
42. crose and non-nutritive sucking into clinical practice while
preterm
infants undergo repeated painful procedures. Thus, when both
sucrose
and non-nutritive sucking can be provided in a unit, the
combination of
them could be recommended as an analgesic alternative for
repeated
pain exposure in preterm infants.
Acknowledgments
We acknowledge the financial contribution of National Natural
Science Foundation of China (81703246), the Preponderant
Discipline
Project of Universities in Jiangsu Province, Nursing Science
Open Fund
of Nanjing University of Chinese Medicine (YSHL2016-018),
Top-notch
Academic Programs Project of Jiangsu Higher Education
Institutions
(PPZY2015C258) and Project of nursing science in Nanjing
University
of Chinese Medicine (NZYHLXPPJG2017-54).
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