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Volume 8, Issue 4, April 2023 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

The Effectiveness of Sucrose as a Pain Reducing


Substance during Procedures in NICU
Dr. Venugopal Reddy. I. Dr. Veera Loknadha Reddy. M.
Medical Director and Consultant Paediatrician, Consultant Paediatrician and Neonatologist,
Ovum Hospital, Bangalore Bangalore.

Abstract:- The medical community has long been aware recently, metabolic screening before being released from the
of infant distress, which typically happens in a hospital hospital. The realisation that both premature and full-term
context. It has become clear that many newborns infants experience pain has brought to light the widespread
admitted to the neonatal critical care unit are not problem of newborns hospitalised in the neonatal critical
receiving enough therapy for stress and discomfort care unit being undertreated for stress and pain1. Improved
because both premature and full-term infants experience management techniques are encouraged by both scientific
pain. The use of enhanced management techniques to and humanitarian principles in order to reduce stress and
decrease stress and pain whenever possible and to offer pain whenever possible and to give timely and effective
fast and effective treatment when suffering cannot be treatment when discomfort cannot be avoided. Present-day
avoided is supported by both scientific and neonates admitted to NICUs are frequently subjected to
humanitarian reasons. At Kasturba Hospital in Manipal, noxious stimuli of varying intensities, including pain,
Karnataka, between October 2012 and September 2013, discomfort, and discomfort. These include both major and
parents of 128 term newborns who had been evaluated small surgical operations, blood draw techniques, and IV
for eligibility took part in the study after giving their cannula insertion. Pain is always a subjective experience.
informed consent. The infants were all congenitally The gold standard for evaluating pain is hence verbalization
healthy and free of abnormalities. of nociceptive sensation2.The detection and management of
pain in newborn newborns in NICUs is currently subpar
According to this study, 24% sucrose performs since neonates cannot verbalise their suffering. In the first
better than 10% dextrose as an analgesic for procedural few weeks of life, infants born at fewer than 32 weeks of
pain in term neonates. The physiological parameters of gestation are subjected to 10 to 15 unpleasant procedures
all 128 neonates were recorded, including heart rate, daily, and in approximately 80% of cases, no pain
oxygen saturation, total cry time, and pain evaluation medication is provided3.
using the NIPS score. Only 78 newborns' salivary
cortisol levels were investigated. The following criteria As in the case of protracted mechanical ventilation and
revealed no discernible differences between the 24% necrotizing enterocolitis, discomfort may be short-term or
sucrose and 10% dextrose in terms of reducing babies' long-term. Even seemingly unimportant carer duties like
procedural pain. The median total cry duration for both diaper changes, daily weighed, and tape removal provide
operations was shorter in the 24% sucrose group than in uncomfortable stimulation. All of these events have a
the 10% dextrose group. detrimental effect on long-term neurologic outcomes,
somatization disorders, and pain sensitivity, especially in
For heel lancing, 24% sucrose significantly preterm neonates. Both scientific and humanitarian
decreased discomfort in 37.5% of infants at 1 minute, considerations support the use of improved management
87.5% of neonates at 3 minutes, and 22.5 seconds vs. 130 approaches to lessen stress and pain whenever possible and
seconds for venipuncture, compared to 10% dextrose. to provide prompt and effective treatment when suffering
This implies that 24% sucrose, as opposed to 10% cannot be avoided.
dextrose, works better as an analgesic for procedural
pain in term babies. Treating pain in infants is essential for a number of
reasons, including decreased oxygenation, hemodynamic
Keywords:- New Borns, Salivary Cortisol, Sucrose, instability, and increased intracranial pressure4.For the
Dextrose, Pain. greatest benefit during unpleasant procedures, the
International Evidence-Based Group for Neonatal Pain
I. INTRODUCTION suggests combining pharmaceutical and behavioural
The length of time it took the medical establishment to therapies5. The combination of oral sucrose and a dummy
acknowledge that infants experience pain is astounding. has been shown to be the best clinically secure and effective
technique for the management of painful operations in
Everyone has the fundamental right to be pain-free, neonates. Salivary cortisol is a good predictor of the health
regardless of their size or age. Pain in newborn infants is a of the hypothalamic-pituitary-adrenal axis. Salivary cortisol
common occurrence. In the hospital setting, infants as has been evaluated in babies subjected to substantial
young as newborns frequently have uncomfortable stressful events, such as painful procedures, and is a useful
procedures. Every infant will experience iatrogenic pain in alternative to blood collection. However, other studies fell
the first few days of life, beginning with the vitamin K short of demonstrating how oral sucrose altered changes in
injection and blood testing for glucose, bilirubin, and more salivary cortisol after painful operations in newborn infants.

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Volume 8, Issue 4, April 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
Therefore, more studies that pinpoint variations in salivary 520) was used to record the entire process. Salivary
cortisol are needed to explain how sucrose affects newborn cortisol was taken before and after the procedure, which is
babies. Little is known about how oral sucrose impacts the covered in more detail in the next section. Two minutes
overall physiological and behavioural stability of infants before the procedure, a 2ml syringe containing 1ml of the
undergoing traumatic procedures, despite the fact that baby solution (A or B) chosen at randomization was injected
pain is a complex issue. In the current investigation, we directly onto the anterior surface of the tongue. Infants
examined physiological (heart rate, oxygen saturation, and consumed the entire amount of sugar or dextrose solution
salivary cortisol) and behavioural (NIPS score and total cry in 45–60 seconds. Venipuncture was performed using a
time) alterations to evaluate pre and post test stress 22G needle on the hand's dorsum, and a heel lance was
responses between a normal procedure with placebo and performed using a 26G needle on the heel's posterolateral
orally administered sucrose solution. surface. The NICU's trained neonatal staff nurses
performed heel lancing, while the NICU's trained
II. MATERIALS AND METHODS residents performed venipuncture. Prior to, one and three
minutes into, and following the procedure, it was
The study was conducted at Kasturba Hospital in calculated what the hear rate, oxygen saturation, and NIPS
Manipal, Karnataka, between October 2012 and September score would be. Before and after the surgery, the total cry
2013. The study was reviewed and approved by the time was calculated. The investigator and a neonatal staff
institutional ethics committee at Manipal's Kasturba member independently evaluated each procedure's NIPS
Hospital. It had CTRI registration. Parents of 128 term score.The face expression (0, 1), cry (0-2), breathing
neonates were examined for eligibility and provided their patterns (0, 1), arms (0, 1), legs (0, 1), and level of arousal
informed permission. In total, 128 neonates were evaluated (0, 1) all contribute to the NIPS score. The overall score is
(64 in the control group and 64 in the experimental group). between 0 and 7. A score higher than three denotes pain
The infants were all congenitally healthy and free of that is clinically serious. To assess consistency among the
abnormalities. raters, an inter rater reliability analysis utilising the Kappa
III. DATA COLLECTION statistic was carried out. It was discovered that the raters'
inter-rater reliability was Kappa = 0.584 (p 0.05), 95% CI
The validity of pain assessment in newborn infants (0.485, 0.685). This suggests that the two observers are in
was improved by examining physiological and behavioural moderate agreement. For the final analysis, the
pain indicators. Data were collected during heel lancing and investigator's NIPS score was used.
venipuncture procedures carried out as part of regular  Saliva collection for cortisol estimation: A cotton swab
clinical treatment for the calculation of glucose and that is rolled at one end and measures 10 cm in length. It
bilirubin, as well as for thyroid function tests, respectively. is sterilised by autoclaving in CSSD and delivered in
The newborns in the control group (n=64) received 10% sterile packets (Figs. 3 and 4). To prevent unintentional
dextrose. A 24% sucrose solution was used by the choking, the neonate's cotton swab was held underneath
experimental group. the tongue for 20 minutes while being closely watched.
 Randomization: The hospital pharmacy provided the Each neonate had two samples taken: one baseline sample
NICU with the test solution (24% sucrose) and the before the surgery and the other sample thereafter, which
placebo solution (10% dextrose) during the trial in was taken at the peak cortisol release time of 20
identical bottles without labels but with the codes A and minutes.No baby cried or displayed any signs of pain
B. Only after the study's conclusion were the codes made during the saliva collection because it was done in a quiet
public. By adopting computer-generated blocked setting. After saliva collection, a sterile medical blade was
randomization, it was possible to conceal allocation while used to cut the cotton swab away from the wooden shaft.
keeping observers' eyes open.The investigator used Using a syringe technique, saliva from the cotton swab
randomization to determine the solution to be was collected and placed in a simple (red) micro
administered to a certain neonate right before performing vacutainer (Figs. 5 and 6). The samples were kept in the
the surgery. biochemistry lab's cold storage at -70 degrees Celsius. In
 Procedure: All operations were carried out as needed the biochemistry lab, salivary cortisol was determined in
when there was a clinical need because cortisol doesn't all of the samples using an ELISA kit (DRG Salivary
have a diurnal rhythm throughout the neonatal period. cortisol HS ELISA kit, SLV-4635, Germany). The
Everything was done one hour after the meal. The amount of cortisol in the saliva was measured in ng/ml.
neonate's wrist was attached to a pulse oxymeter (Philips The normal reference range for salivary cortisol is 3.4–
vital signs MP 20) monitor to record the pulse rate and 23.45 ng/ml, with a mean and standard deviation of
oxygen saturation with the least amount of disruption to 10.71–6.58 ng/ml75.
the baby's routine. A cellphone camera (Nokia Lumia

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Volume 8, Issue 4, April 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165

Fig. 1: Sterile cotton swab rolled on a thin wooden stick

Fig. 2: sterile cotton swabs in a sterile packet

Fig. 3: saliva extraction step 1 Fig 4: saliva extraction step 2

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Volume 8, Issue 4, April 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
 Statistical Analysis: The statistical analyses were carried groups using the Mann-Whitney U test. Based on NIPS
out using SPSS for Windows (version 16.0, SPSS Inc, scores, the samples were divided into two groups: less
Chicago, IL, USA). To compare demographic traits, the than 4 and greater than or equal to 4 because a score of 4
mean, standard deviation, frequency, independent t-test denotes clinically severe pain. The proportions of these
for continuous data, and 2 test for categorical data were all values at 1 and 3 minutes following surgery were
employed. The differences in heart rate, oxygen compared using the Fisher exact test.
saturation, and salivary cortisol % were assessed before  Codes are revealed: The principal chemist released the
the procedure, after it started, and three minutes codes following the investigation and analysis.
afterwards. The Mann-Whitney U test was used to  Code A = 10% Dextrose
compare these numbers between the two groups. Cry  Code B = 24% Sucrose
length and NIPS Score were compared between the two

Assessed for eligibility (n=160)


Enrollment

Excluded (n=32)
-Parents refused to give
Consent

Randomization

Randomized (n=128)

Allocation

Allocated to 10% Dextrose group Allocated to 24% Sucrose group (n=64)


(n=64)
Received solution B (n=64)
Received solution A (n=64)

Analysis

Analyzed (n=64) Analyzed (n=64)

Venipuncture (n=32) Venipuncture (n=32)

Heel prick (n = 32) Heel prick (n = 32)

Fig. 5: Consort flow diagram

IV. RESULTS AND DISCUSSION  NIPS score


 Crying behavior:
The results were interpreted between the experimental  Total cry time
and control groups with the following parameters.
 Demographic characteristics There were 128 neonates randomly assigned, 64 to
 Physiological parameters: each group. All 128 neonates had their physiological
 Heart rate measurements taken, including heart rate, oxygen saturation,
 Oxygen saturation total cry time, and pain assessment using the NIPS score.
 Biochemical parameters: However, because there were insufficient samples, salivary
 Salivary cortisol cortisol was only examined in 78 neonates. The findings and
 Pain Assessment: discussion are listed below.

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Volume 8, Issue 4, April 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
A. DEMOGRAPHIC CHARACTERISTICS

Table 1: Demographic characteristics


10% Dextrose 24% Sucrose
Variable p value*
(n=64) (n=64)

Gender (male/female) 32/32 33/31 0.860

Birth weight(gm) 2955 ± 435 2826 ± 514 0.213

Gestational age(weeks) 38.2 ± 1.0 38.1 ± 1.0 0.732

Postnatal age (hours) 69.0 ± 46.5 68.4 ± 38.5 0.105

Mode of delivery(VD/LSCS) 17/47 23/41 0.253


Apgar score at 5 min 9 9

2
Data are expressed as number or mean ± SD (standard
χ test for categorical data.
deviation)
The experimental group and the control group did not
*
p value corresponds to results of independent t-test differ significantly in any of the demographic variables.
for continuous data and

B. PHYSIOLOGICAL PARAMETERS

 HEART RATE(HR) BEFORE AND DURING THE PROCEDURE:

Table 2: Comparison of heart ratebefore and during the procedures between the groups
Procedure Solution HR before HR at *p value HR *p value
received procedureMean t=1minMean att=3minMean
± SD ± SD ± SD
Heel lance 10% Dextrose 138 ± 14 142 ± 17 0.327 137 ± 19 0.626
(n=64) (n=32)
24% Sucrose 140 ± 12 148 ± 16 138 ± 23
(n=32)
Venipuncture 10% 133 ± 13 146 ± 22 0.340 148 ± 26 0.155
(n=64) Dextrose(n=32)
24% 133 ± 15 149 ± 18 139 ± 28
Sucrose(n=32)
*p value corresponds to Mann-Whitney U test Heart rate expressed as beats per minute.

 Heel lance: The mean heart rate rose in both groups one Succrose considerably decreased heart rate as
minute after the heel lance procedure, but it fell three compared to the control group (sterile water) in numerous
minutes later. The heel lance's exceptionally quick-acting previous experiments conducted by Bucher HU et al.80,
discomfort, which for most babies lasts between 30 and a Ramenghi LA et al., and Ors R et al.
minute, is the cause of this disparity. The heart rates were
similar in both groups. The percentage differences  Venipuncture: At one minute after the procedure, the
between the heart rates prior to surgery and at 1 and 3 mean heart rate in both groups increased during the
minutes following it were calculated using the Mann- venipuncture technique. However, the heart rate in the
Whitney U test. There were no statistically significant 24% sucrose group is lower after 3 minutes after the
differences in heart rate between 24% sucrose and 10% surgery, while it is higher in the 10% dextrose group. This
dextrose for the heel lance procedure. discrepancy results from the pain, which lasts for two to
three minutes. It is likely that sucrose reduced the pain
There were no discernible variations in heart rate and, as a result, the heart rate three minutes after the
between the sucrose group and the control group (sterile treatment. We used the Mann-Whitney U test to calculate
water or no treatment) in the trials conducted by Kyounget the percentage differences between the heart rates before
al. and Isik U et al. the procedure and at 1 and 3 minutes after it. According to
statistics, there were no appreciable variations in heart rate

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Volume 8, Issue 4, April 2023 International Journal of Innovative Science and Research Technology
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during venipuncture between 24% sucrose and 10% In studies by Abad et al, Acharya et al, sucrose
dextrose. significantly reduced heart rate compared to control group.

 OXYGEN SATURATION (SpO2) BEFORE AND DURING THE PROCEDURE:

Table 3: Comparison of oxygen saturation before and during the procedures between the groups.
Procedure Solution SpO2 before SpO2 at * p value SpO2 att=3 *P value
received procedureMean t=1minMean ± minMean ±
± SD SD SD
Heel lance(n=64) 10% 98.3 ± 2 95.4 ± 4.3 0.543 95.5±5.3 0.253
Dextrose(n=32)
24% 97.8± 2.3 95.6 ± 4.1 96.2±4.4
Sucrose(n=32)
Venipuncture(n=64) 10% 97.7± 2.2 93.0± 7.0 0.727 93.0±6.0 0.535
Dextrose(n=32)
24% 98.0 ± 1.8 94.0± 7.2 94.3±8.3
Sucrose(n=32)
*P value Mann-Whitney U test
 Heel lance: For heel lance, there were no appreciable  Venipuncture: For venipuncture, there were no
changes in the means of oxygen saturation between 24% appreciable variations in oxygen saturation between 24%
sucrose and 10% dextrose. We used the Mann-Whitney U sucrose and 10% dextrose. We used the Mann-Whitney U
test to calculate the percentage differences between the test to calculate the percentage differences between the
SpO2 levels prior to the surgery and at 1 and 3 minutes SpO2 levels prior to the surgery and at 1 and 3 minutes
after it. In terms of SPO2 for the heel lance operation, after it. Statistics revealed no significant variations in
there were no statistically significant changes between SpO2 during venipuncture between 24% sucrose and 10%
24% sucrose and 10% dextrose. dextrose.

There were no appreciable variations in SpO2 between There were no discernible variations in SpO2 between
the sucrose group and the control groups in the the sucrose and control groups in the research by Rush et al.
investigations by Overgaard C et al., Harrison D et al, (1992), Yilmaz F et al. (1993), and Ogawa S et al. (1994).
Mathai S, and Okan F.
There are no studies that demonstrate appreciable
There was a considerable drop in SpO2 in the sucrose variations in oxygen saturation between the sucrose group
group compared to breast feeding group, according to a and the control group during venipuncture.
study by Codipeitro et al.11.

C. BIOCHEMICAL PARAMETERS

 SALIVARY CORTISOL BEFORE AND AFTER THE PROCEDURE

Table 4: Comparison of salivary cortisol before and after the procedures between the groups
Procedure Solution Salivary cortisol before Salivary cortisol after *p value
received procedure procedure
Mean ± SD Mean ± SD
Heel lance 10% Dextrose 18.1 ± 9.0 20.1 ± 8.3 0.820
(n=40) (n=20)
24% Sucrose 14.1 ± 8.6 17.3 ± 9.8
(n=20)
Venipuncture 10% Dextrose 16.4 ± 8.4 17.9 ± 7.4 0.593
(n=38) (n=20)
24% Sucrose 14.1 ± 9.2 15.5 ± 9.6
(n=18)
*p value corresponds to Mann-Whitney U test

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Volume 8, Issue 4, April 2023 International Journal of Innovative Science and Research Technology
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 Heel lance: There were no discernible differences Studies that evaluated the salivary cortisol levels
between the salivary cortisol levels assessed before and between the sucrose group and the control group using 10%
after the heel lance operation using 24% sucrose and 10% dextrose for the heel lance found no discernible differences.
dextrose. The percentage differences in salivary cortisol
levels before and after the operation were calculated using Salivary cortisol levels before and after venipuncture
the Mann-Whitney U test. For the heel lance method, in the presence of 24% sucrose and 10% dextrose did not
there were no statistically significant differences in differ substantially. The percentage differences in salivary
salivary cortisol levels between 24% sucrose and 10% cortisol levels before and after the operation were calculated
dextrose. using the Mann-Whitney U test. There were no statistically
significant differences between 24% sucrose and 10%
In two studies by Kyoung et al.56 and Greenberg et dextrose in terms of SPO2 for the heel lance procedure.
al.95, there were no observable differences between the two Salivary cortisol levels during venipuncture have not been
groups. studied.

D. PAIN ASSESSMENT

 NIPS SCORES BEFORE AND DURING THE PROCEDURES

Table 5: Comparison of NIPS score at 1 min and 3 min after procedure between the groups

NIPS at NIPS at
Solution
Procedure t=1 min *p value t=3min *p value
received
Median(Q1,Q3) Median(Q1,Q3)

10% Dextrose
7(3,7) 0(0,3.7)
(n=32)
0.
Heel lance(n=64) 0.814
059
24% Sucrose
7(2,7) 0(0,0)
(n=32)

10% Dextrose
7(5,7) 6(0,7)
(n=32)
Venipuncture 0.
0.102
(n=64) 190
24% Sucrose
7(2,7) 1(0,7)
(n=32)
*p value corresponds to Mann – Whitney U test

Fig. 6: Box plot showing Median NIPS scores at 1 min and at 3 min for Heel lance. The line inside the box represents the median
NIPS score and the colored area represents the inter quartile range

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X axis: Solution received ; Y axis: NIPS score,  Heel lance: The 24% sucrose and 10% dextrose groups
Procedure: Heel lance did not significantly vary in NIPS scores at 1 or 3
minutes.
Blue: NIPS score at 3 minutes post procedure
Green:NIPS score at 3 minutes post procedure There was a substantial decline in NIPS scores for the
sucrose group in studies by Kyong et al.16, Overgaard et
al.27, and Yilmaz et al.33 as compared to the control group.

Fig. 7: Box plot showing Median NIPS scores at 1 min and at 3 min for venipuncture. The line inside the box represents the
median NIPS score and the colored area represents the inter quartile range

X axis: Solution received ; Y axis: NIPS score, score at 3 minutes for the 10% dextrose group was 6 and
Procedure: Heel lance the median NIPS score for the 24% sucrose group was 1.
This shows that 3 minutes after the surgery, 24% sucrose
Blue: NIPS score at 3 minutes post procedure is effective in reducing discomfort. The groups did not,
however, vary statistically significantly. No studies
Green:NIPS score at 3 minutes post procedure employing the NIPS score for venipuncture have been
published.
 Venipuncture: While the median NIPS scores at 1 and 3
minutes were similar for both groups, the median NIPS

Table 6: Comparison between the 10% Dextrose and 24% Sucrose groups for the number of newborns with an NIPS score of 4 at
1 minute and 3 minutes following the procedure.
NIPS score<4 at t=1min NIPS score<4 at t=3min
10% 24% Sucrose 10% 24% Sucrose *
Procedure Dextrose(n=32) (n=32) *p value Dextrose(n=32) (n=32) p value
Heel lance(n=32) 9 12 0.595 24 28 0.337
Venipuncture
(n=32) 5 12 0.088 14 21 0.131
*p value corresponds to Fischer Exact test.

At 1 and 3 minutes into the procedure, there were 10% dextrose. However, when the Fischer exact test was
more infants who received sucrose and received an NIPS employed to compare the groups, there were no statistically
score of 4 than there were when 10% dextrose was utilised. significant differences between 24% sucrose and 10%
Therefore, 24% sucrose has a better analgesic impact than dextrose.

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Volume 8, Issue 4, April 2023 International Journal of Innovative Science and Research Technology
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E. CRYING BEHAVIOR

 TOTAL CRY TIME DURING THE PROCEDURE:

Table 7: Comparison of Total cry time during procedure between 10% Dextrose and 24% Sucrose groups
Procedure Total Cry Time during procedure (in seconds) *p value
10% Dextrose 24% Sucrose
(n=64) (n=64)
Median(Q1Q3) Median(Q1Q3)
Heel lance(n=64) 37.5(2.7,63.7) 10(0,54) 0.16
Venipuncture 130(18.7,180) 22.5(0,180) 0.11
(n=64)
*p value corresponds to Mann-Whitney U test.

Fig. 8: Box plot showing Median Total cry time for both the groups for heel lance procedure

 Heel lance: When compared to the dextrose group, the that sucrose reduced the amount of time babies spent crying
sucrose group's total cry time was much lower (median 10 overall compared to the control group. In other
sec). However, statistically speaking, there was no investigations by Harrison et al.88, Mathai et al.29, and
change. Ogawa et al.34, the sucrose group's cry time was not
significantly shorter than that of the control group.
Researchers Kyoung et al.16, Isik U et al.19, Bucher
HU et al.80, Ramenghi LA et al.11, and Ors R et al.12 found

Fig. 9: Box plot showing Median Total cry time for both the groups for venipuncture procedure

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 Venipuncture: When compared to the dextrose group procedures.Cochrane Database Syst Rev. 2013 Jan
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