Background - Methods - Results - Characteristics of Included Studies - References - Data Tables & Graphs
Janet Yamada
Literature search and identification of trials for inclusion
Evaluation of methodologic quality of included trials
Abstraction and meta-analysis of data
Verifying and entering data into RevMan
Writing of text of review
Arne Ohlsson
Literature search and identification of trials for inclusion
Evaluation of methodologic quality of included trials
Abstraction of data
Verifying and entering data into RevMan
Writing of text of review
Newborn babies undergoing painful procedures need help to have their pain reduced. This is done routinely for major procedures but may not be done for tests (such as taking blood) or needles. Drugs can be used to reduce pain but there are several other methods including sucking a pacifier with or without sucrose (sugar). The review of trials found that giving sucrose to babies decreases their crying time and other pain indicators such as facial action. More research is needed into the effect of repeated doses of sucrose, especially for very low birthweight or ventilated babies.
Statistical Analysis
The statistical package (RevMan 4.1) of the Cochrane Collaboration
was used. For meta-analysis, a weighted mean difference (WMD) with 95%
confidence intervals (CI) using the fixed effects model was reported for
continuous outcome measures.
The use of repeated administrations of sucrose in neonates needs to be investigated as does the use of sucrose in combination with other behavioural (e.g., facilitated tucking, kangaroo care) and pharmacologic (e.g., morphine, fentanyl) interventions. Use of sucrose in neonates who are of very low birth weight, unstable and/or ventilated also needs to be addressed.
A wide variety of pharmacologic and nonpharmacologic interventions are available for management of pain in infants. Pharmacologic interventions are infrequently employed for procedural pain due to concerns about adverse effects and a lack of conviction that pain is important to the infant's present or future well being. Nonpharmacologic interventions are more feasible alternatives as concerns about the risk of adverse effects is minimal.
The administration of sucrose with and without non-nutritive sucking (pacifiers) has been the most frequently studied nonpharmacologic intervention for relief of procedural pain in neonates. Sucrose has been examined for its calming effects in crying newborns (Barr 1993, Barr 1994, Haynes 1995, Smith 1992) and its pain-relieving effects for invasive procedures in term and preterm neonates (Stevens 1997a). The effects of sucrose and non-nutritive sucking are thought to be mediated by both the endogenous opioid and non-opioid systems (Gunnar 1988) but the underlying mechanisms may differ. These mechanisms may be additive or synergistic but most likely depend on normal functioning of central mechanisms. In a systematic review/meta-analysis of the efficacy of sucrose for procedural pain management, Stevens (Stevens 1997a) found that proportion of time crying was decreased with 0.24 - 0.48 g (2ml of a 12-24% sucrose solution) administered orally 2 minutes prior to a painful procedure (heel lance or venepuncture). The current update of this systematic review is justified as additional randomized controlled trials (RCTs) have been published since the previous Cochrane review (Stevens 1998).
Standard methods of the Neonatal Collaborative Review Group were used to assess the methodological quality of the included trials. The questions asked regarding quality were 1) Blinding of randomization? 2) Blinding of intervention? 3) Complete follow-up? 4) Blinding of outcome measurement? There were three possible answers to these questions; Can't tell, yes and no. The methodological quality of each study was assessed independently by three reviewers, who were not blinded to trial authors or institutions.
Methods to collect data from the included trials: three authors abstracted data separately; these were compared and differences were resolved. Additional data were provided by investigators in two studies (Johnston 1999a, Stevens 1999).
Statistical Analysis
The statistical package (RevMan 4.1) provided by the Cochrane Collaboration
was used. For meta-analysis, a weighted mean difference (WMD) with 95%
confidence intervals (CI) using the fixed effects model was reported for
continuous outcome measures.
Of the seventeen studies in this review, nine studies evaluated term infants, seven studies evaluated preterm infants and one study included both preterm and term infants. The majority of infants received a heel lance as the painful procedure (n = 15 studies). In two studies, infants received a venepuncture. Of the twelve studies that evaluated cry behaviour, eight studies (including 549 infants) reported information on the outcome of time crying over three minutes but could not be combined as means and standard deviations were not provided. Eleven studies assessed the effect of sucrose on changes in heart rate. Four studies evaluated oxygen saturation changes (two of these studies also measured respiratory rate changes). One study assessed the intensity of sucking in infants who received sucrose compared to those who received water. One study measured facial grimacing in infants to evaluate pain. Six studies used multidimensional behavioural pain measures while four studies used multidimensional composite pain measures. For the three studies that evaluated pain as a composite score using the Premature Infant Pain Profile (PIPP) at 30 seconds and 60 seconds after heel lance, means and standard deviations were provided in one of the studies (Gibbins 2001) and obtained from the authors for the two remaining studies (Johnston 1999a, Stevens 1999). Two studies reported the percent changes in heart rate at one and three minutes after heel lance. Means and standard errors of the mean were reported for both studies (Haouari 1995, Isik 2000a). Standard errors were converted to standard deviations. Only four of the 17 studies evaluated adverse effects.
In terms of whether the method of randomization was concealed, 6 studies (35%) adequately reported allocation concealment (scored as "A" under included studies table) and 11 studies (65%) did not clearly report this (scored as "B" under included studies table).
Few studies provided a definition of pain or how it was conceptualized in relation to the outcomes. There were also differences in study methods. The majority of studies utilized heel lance as the pain stimulus. However, little detail about this procedure was provided. Therefore, it is impossible to know if the painful stimuli were comparable in intensity, duration or frequency. The length of infant observation following the heel lance was not reported frequently. This may have implications for the incidence of adverse effects.
The delivery method of sucrose differed between studies (syringe, NG-tube, dropper or pacifier). Outcomes were reported inconsistently; as means with SD or SE, medians with ranges, and often in graph form without providing actual numbers.
Behavioural Outcomes
1. Cry Behaviour
Of the 12 studies that evaluated cry behaviour in term and preterm
neonates, all but one study (Rushforth 1993) found significant reductions
in crying in the sucrose groups. In these 11 studies, seven studies evaluated
time crying during three minutes after a painful procedure (Abad 1993,
Blass 1999, Gormally 2001, Haouri 1995, Isik 2000, Ors 1999, Ramenghi 1996b).
Doses of as little as 0.25 ml of 24% sucrose (Gormally 2001) to as high
as 2ml of 50% sucrose (Ramenghi 1996b) reduced cry behaviour three minutes
after venepuncture or heel lance. In the study by Abad (1996), cry duration
was significantly reduced in the group receiving 2ml of 24% (0.48g) sucrose
at three minutes after venepuncture compared to water (p < 0.05) but
not in the group receiving 2ml of 12% (0.24g). Haouri (1995) assessed total
crying time over three minutes using 2ml of 12.5% (0.25g) sucrose, 2ml
of 25% (0.5g) sucrose and 2ml of 50% (1.0g) sucrose. Results showed a reduction
in total crying time and the time of first cry (p < 0.02), median time
crying at the end of the first and second minutes in the group receiving
2ml of 50% (1.0g) sucrose compared to the control group (p < 0.02 and
p = 0.003, respectively). In the second minute, duration of cry was also
lower in the group receiving 2ml of 25% (0.5g) sucrose compared to the
control group (p = 0.02). The study by Overgaard (1999) evaluated various
measures of cry behaviour and reported significant reductions in cry behaviour
for the group receiving 2ml of 50% (1.0g) sucrose compared to the control
group. Cry behaviour was also reduced over five minutes after heel lance
in infants who received sucrose compared to the control groups (Ramenghi
1996a, Ramenghi 1999). Duration of first cry was also lower in the groups
receiving sucrose compared to the control groups (Ramenghi 1996a, Ramenghi
1999).
2. Quality of Sucking
The one study, by Ramenghi (1996a), that assessed the quality of sucking
in preterm infants found that the quality of sucking was significantly
more intense in infants who received 1ml of 25% (0.25g) sucrose compared
to those who were in the control group (p = 0.04).
3. Grimace
The one study by, Blass (1999), that evaluated percent time grimacing
in term infants undergoing heel lance found reduced grimacing in infants
who received 2ml of 12% (0.24g) sucrose alone compared with water (p =
0.0003) and sucrose with pacifier compared to water alone (p = 0.002) and
water with pacifier (p = 0.04).
Physiologic Outcomes
1. Heart Rate/Vagal Tone
Of the 11 studies measuring heart rate/vagal tone, sucrose had a significant
effect in reducing heart rate in seven studies (Abad 1993, Blass 1999,
Bucher 1995, Gormally 2001, Hauoari 1995, Ors 1999, Ramenghi 1996b). When
results for change in heart rate were pooled for two of these studies (Haouari
1995, Isik 2000a), there was statistically significant heterogeneity found
between studies at one minute after heel lance and no heterogeneity between
studies at three minutes after heel lance. There were no significant differences
in per cent change in heart rate for infants given sucrose (dose range
0.5 g to 0.6 g) compared to the control group, [WMD 0.90% (95% CI -5.81,
7.61); p = 0.8] at one minute and [WMD -6.20% (95% CI -15.27, 2.88); p
= 0.18] at three minutes after heel lance. The one study that assessed
vagal tone (Gormally 2001) reported no significant main effects.
2. Oxygen Saturation/Respiratory Status
None of the studies that assessed the effects of sucrose on oxygen
saturation and respiratory rates reported significant differences between
groups.
Multidimensional Behavioural Pain Measures
Of the six studies that used multidimensional behavioural pain measures, five studies (Carbajal 1999, Johnston 1997a, Ramenghi 1996a, Ramenghi 1996b, Ramenghi 1999) found significant results in favour of sucrose. In the study by Carbajal (1999), pain was measured using the Douleur Aigue du Nouveau-ne (DAN) scale, which assesses facial expression, limb movements and vocal expression. Although this study reported significantly lower pain scores in all intervention groups compared to the control group, there were also lower pain scores for the infants who were given a pacifier alone compared to the groups who received glucose or 30% sucrose (p = 0.0001). Johnston (1997a) measured pain using the Neonatal Facial Coding System which includes 10 facial actions and found that the groups receiving 0.05ml of 24% (0.012g) sucrose and combined sucrose with rocking had decreased facial actions compared to the control group (p < 0.02). The three studies by Ramenghi (1996a, 1996b, 1999) measured pain using their own pain scale that included four facial expressions and the presence of cry. Sucrose doses used ranged from 1ml of 25% (0.25g) sucrose to 2ml of 50%(1.0g) sucrose. Pain scores were significantly lower in the groups that received sucrose compared to the control groups.
Multidimensional Composite Pain Measures
Three studies used the Premature Infant Pain Profile (PIPP) to evaluate
pain (Gibbins 2001, Johnston 1999a, Stevens 1999). The PIPP is a validated
pain measure that includes behavioural ( three facial actions), physiologic
(heart rate and oxygen saturation) and contextual indicators(gestational
age and behavioural state). When PIPP scores were pooled across three studies
(Gibbins 2001, Johnston 1999a, Stevens 1999), there was no statistically
significant heterogeneity found. PIPP scores were significantly reduced
in infants who were given sucrose (dose range 0.012 g to 0.12 g) compared
to the control group, [WMD -1.64 (95% CI -2.47, - 0.81); p = 0.0001] at
30 seconds and [WMD -2.05, (95% CI -3.08, -1.02); p = 0.00010] at 60 seconds
after heel lance. In the study by Overgaard (1999), the Neonatal Infant
Pain Scale (NIPS), composed of behavioural and physiologic indicators,
was used to assess pain in infants receiving 2ml of 50% (1.0g) sucrose
compared to water. NIPS scores were significantly lower in the group receiving
sucrose compared to the control group.
Adverse Effects
Of the four studies that evaluated adverse effects (Carbajal 1999,
Gibbins 2001, Ramenghi 1996a, Stevens 1999), one study by Gibbins 2001
reported side effects in infants. In this study, minor adverse effects
were found in six infants. None of the adverse events occurred in the sucrose
with pacifier group. One neonate who received water with pacifier choked
when administered the water and stabilized within 10 seconds. Three infants
randomized to the sucrose group and two infants randomized to the water
with pacifier groups desaturated when the study intervention was administered.
Each neonate recovered spontaneously with no medical interventions required.
Sucrose administration was also associated with decreases in heart rate, facial actions and motor activity during the immediate post stimulus period. When results for percent change in heart rate at one minute and three minutes after heel lance were pooled for two studies, there was no significant difference between groups. For the studies that evaluated oxygen saturation and respiratory rates, there were no significant effects of the interventions found in each of the studies.
Different concentrations of sucrose administered at varying time intervals have indicated that the greatest analgesic effect is realized when sucrose is administered approximately two minutes before the painful stimulus. This interval is thought to coincide with endogenous opioid release. Adverse effects were evaluated in four studies. In the study that most carefully observed for adverse events (Gibbins 2001), only 6 infants (3%) experienced minor side effects (e.g., oxygen desaturation, choking) which did not require any intervention. It is not clear whether investigators in the other three studies carefully monitored for adverse effects or for how long. Reporting on the incidence of any adverse effects of single or repeated administration of sucrose of various concentrations needs to be undertaken in both term and preterm infants. One group of investigators, 25 years ago, reported that frequent (8-12 times per day) small volumes (0.5-1 ml) of 20% sucrose concentration (mixed with calcium lactate given 20 minutes prior to gavage feeding) could be a contributor to necrotizing enterocolitis (NEC) in very low birth weight infants (Willis 1977). This finding was hypothesized to be the result of the hyperosmolality of the undiluted calcium lactate solution that led to local trauma to the upper gut wall, initiating the pathological process resulting in NEC. Since the methodologic rigor of this study was somewhat questionable, specific attention to the efficacy and the safety of sucrose administration in very-low-birth-weight preterm infants needs to be considered.
Of the 17 studies included in this review, nine included term neonates, seven included preterm neonates and one study included both term and preterm neonates. Generally, the babies were healthy and stable and very few were less than 27 weeks gestational age at birth. Although the preterm infant's pain response is generally consistent with that of the term infant, it is often more subtle, less sustained and affected by the infant's behavioural state and severity of illness. There was no significant difference in this systematic review between the cry outcomes in term and preterm infants; however, the incidence of crying following painful stimuli has been reported to be 50% less in preterm infants as compared to term infants in other research (Stevens 1994), therefore not making it a reliable indicator of pain in this population. We have limited knowledge of what dose of sucrose or administration method provides the least risk for less healthy preterm infants and very low birth weight infants (Gibbins 2001).
The strength of the studies reviewed was in the design. Most were carefully planned prospective randomized controlled clinical trials with a control group and one or more treatment interventions. Ten studies were not double-blinded as additional interventions (e.g., use of pacifiers) were utilized that precluded blinding. Several studies could not be included as the methods of allocation and/or the number of infants in each condition (intervention group) were not clearly stated. Methods of blinding of randomization frequently were not reported. Attempts to obtain missing information were generally met with limited success.
There were both conceptual and methodological limitations in the studies that were identified in the systematic review. Few studies provided a definition of pain or how it was conceptualized in relation to the outcomes. If the reported outcomes reflect the investigators' conceptualization of pain, then we can assume that most investigators considered proportion, percentage or duration of time crying to be the most valid indicator of pain in neonates. Few investigators used composite pain assessments or multidimensional approaches to pain measurement that reflect a more comprehensive conceptualization of pain. Although research on infant cry has delineated certain cry characteristics such as pitch, intensity, melody and harmonics as being good indicators of pain, these were not assessed in the sucrose studies reviewed. Cry duration may give some indication of distress. However, alone, it does not necessarily confirm or deny that the infant is in pain. For unstable and ventilated infants who do not cry following painful procedures, cry may be an inappropriate outcome. Recent research suggests that a multivariate approach or composite pain score including physiologic, behavioural and contextual indices would be a more valid measure of pain (Stevens 1997c).
There were also differences in study methods. The majority of studies utilized heel lance as the pain stimulus. However, little detail about this procedure was provided. Therefore, it is impossible to know if the painful stimuli (or painful procedures) were comparable in intensity, duration or frequency. Preparation for the heel lance through heel warming, and soothing interventions throughout the procedure such as containment or positioning, could provide comfort to the infant and act as co-interventions. The length of infant observation following the heel lance was not reported frequently. This lack of methodologic standardization may have implications for the incidence of adverse effects.
The delivery method of the sucrose was variable between studies. Sucrose was delivered to the infant by syringe, dropper or pacifier. The pacifier promotes non-nutritive sucking and calming that may also contribute to reducing pain-elicited distress (Campos 1994). Blass (1994) suggests that sucking exerts a profound behavioural effect and induces feelings of calm. Other researchers have found that non-nutritive sucking reduces heart rate and metabolic rate, causes infants to bring their hands to their mouths and elevates the pain threshold. However, contact has not been shown to affect cortisol response, heart rate, vagal tone and oxygen saturation (DiPietro 1994; Gunnar 1992). The calming effects have not been sustained following cessation of the contact. This is in contrast to sucrose administration where the effects persist beyond the cessation of contact for several minutes. Blass and Hoffmeyer (Blass 1991) examined the combined effectiveness of sucrose and pacifiers for relieving procedural pain in neonates and reported that physiologic and behavioural changes resulted from both sucrose and non-nutritive interventions. More research addressing the analgesic and calming effects of sucrose and their interaction needs to be undertaken to increase understanding of the underlying mechanisms of sucrose and pain relief in the infant.
There were no major changes made to the methods used for this systematic review. Some minor refinements to the inclusion criteria for this review were made (e.g., intramuscular injections were not included as a painful procedure; abstracts were not included). Otherwise, standard review procedures were followed for the present review, as for the previous review.
In summary, studies in this review generally support the efficacy and safety of sucrose for reducing pain from single heel lance and venepuncture for neonates. However, one study (Carbajal 1999) supported the efficacy of a pacifier over sucrose. Additional research is required to better determine the efficacy and safety of sucrose for repeated administration used alone and in combination with other pharmacologic and nonpharmacologic interventions.
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Abad 1996 | Double blind, randomized controlled trial
I Blinding of randomization - can't tell II Blinding of intervention - yes III Complete follow-up - yes IV Blinding of outcome measurement - yes |
28 (29 - 36 weeks gestational age) infants, postnatal age 1-26 days | 2ml of 12% sucrose via syringe (n = 8) 2 min prior to venepuncture
(n = 8).
2ml of 24% sucrose via syringe (n = 8) 2 min prior to venepuncture (n = 8). 2ml of spring water via syringe (n = 12) 2 min prior to venepuncture (n = 12). |
Oxygen saturation, respiratory rate, heart rate (just before and just after administering the solution and 5 min after venepuncture), time spent in audible crying for three min following venepuncture. | One-way and two-way ANOVA used to evaluate outcomes
Data were reported as means and standard deviations for the three physiologic outcomes and as medians and interquartile ranges for cry duration. Data were collected at three time points; just before the administration of the solution, just after the solution and 5 minutes after venepuncture. Adverse effects - were not evaluated |
B |
| Blass 1999 | Randomized controlled trial
I Blinding of randomization -can't tell II Blinding of intervention - yes, for some comparisons III Complete follow-up - yes IV Blinding of outcome measurement - yes, blinded for some interventions |
40 term newborn infants, 34 - 55 hours old | 2ml of 12% sucrose over two minutes via syringe (n=10)
2ml of water via syringe over 2 minutes (n=10) Pacifier dipped every 30 seconds in 12% sucrose solution for two minutes (n=10) Pacifier dipped in water every 30 seconds for two minutes (n = 10) prior to heel lance |
Percentage of time spent crying 3 minutes after heel lance. Percentage of time spent grimacing, change in mean HR | Data were reported in graph forms only.
Results of ANOVA reported as p-values only (We have contacted the authors to obtain additional information) Adverse effects: were not evaluated |
B |
| Bucher 1995 | Randomized, double blind, placebo controlled cross over trial.
I Blinding of randomization - yes II Blinding of intervention - yes III Complete follow-up - yes IV Blinding of outcome measurement - yes |
16 preterm infants (27 - 34 weeks gestational age), postnatal age approximately 42 days | 2ml of 50% sucrose via syringe into the mouth 2 minutes before heel
lance.
2ml of distilled water via syringe into the mouth 2 minutes before heel lance. (n = 16, cross over design). |
Increase in HR (bpm); Recovery time for HR (sec); recovery time for respirations (sec); crying (percent of total intervention); recovery time until crying stopped (sec); tcpO2 (max increase -kPa); tcpO2 (max decrease -kPa); tcpO2 (difference between baseline and 10 minutes after end of intervention -kPa); tcpCO2 (max decrease -kPa); tcpCO2 (difference between baseline and 10 min after the end of intervention). | Results were presented in graph forms without mean values and standard
deviations and/or in tables with medians with interquartile ranges. Wilcoxon
signed rank test
Adverse effects - were not evaluated |
A |
| Carbajal 1999 | Randomized controlled trial
I Blinding of randomization - yes II Blinding of intervention - no III Complete follow-up - yes IV Blinding of outcome measurement - no |
150 term newborn infants, 3-4 days old | No treatment (n = 25)
2 ml of sterile water via syringe over 30 seconds (n = 25) 2 ml of 30% glucose via syringe (n = 25) 2 ml of 30% sucrose (n = 25) Pacifier alone (n = 25) 2 minutes prior to venepuncture 2 ml of 30% sucrose via syringe followed by sucking a pacifier (n = 25) |
Douleur Aigue du Nouveau-ne (DAN) scale | Mann-Whitney U test used to evaluate pain scores
Adverse effects: were evaluated |
A |
| Gibbins 2001 | Randomized controlled trial
I Blinding of randomization - yes II Blinding of intervention - no III Complete follow-up - yes IV Blinding of outcome measurement - yes |
190 preterm and term infants, mean gestational age of 33.7 weeks, under 7 days post natal age | 0.5ml of 24% sucrose via syringe to the anterior surface of the tongue
followed by pacifier (n=64)
0.5ml 24% sucrose without pacifier (n=62) 0.5ml sterile water with pacifier (n=64) 2 minutes prior to heel lance |
Premature Infant Pain Profile (PIPP) at 30 and 60 seconds after heel lance | One-way ANOVA to evaluate mean pain scores.
Results were reported as means and standard deviations Adverse effects: were evaluated |
A |
| Gormally 2001 | Randomized controlled trial, factorial design
I Blinding of randomization - can't tell II Blinding of intervention - coders were blind to infant assignment but not to holding condition III Complete follow-up - yes IV Blinding of outcome measurement - yes |
94 normally developing newborns, mean gestational age 39.4 weeks on
2nd or 3rd day of life
Nine infants did not complete the study due to early discharge, nurse or testing room unavailability to obtain heel stick, infant removed from study prior to start date, technical difficulties. |
No holding and sterile water given by pipette (n=21)
No holding and 0.25 ml of 24% sucrose solution (0.06g) given by pipette (n=22) Holding and sterile water given by pipette (n=20) Holding and 0.25 ml of 24% sucrose solution (0.06 g) by pipette (n=22) All solutions given 3 times at 30 second intervals |
Percentage of time crying
Pain concatenation scores for facial activity Mean heart rate Mean vagal tone index Measurements at preintervention, 1, 2, and 3 minutes after heel lance |
Factorial ANOVA to assess effects on behavioural and physiological
measures No means or standard deviations reported Adverse effects: were not evaluated |
B |
| Haouari 1995 | Randomized, double blind placebo controlled trial
I Blinding of randomization - can't tell II Blinding of intervention - yes III Complete follow-up - yes IV Blinding of outcome measurement - yes |
60 term (37-42 weeks gestation) infants. 1-6 days of age. | 2ml of 12.5% sucrose 2 minutes prior to heel lance (n = 15)
2 ml of 25% sucrose 2 minutes prior to heel lance (n = 15). 2 ml of 50 % sucrose 2 minutes prior to heel lance (n = 15). 2ml of sterile water 2 minutes prior to heel lance (n = 15). All solutions were given by syringe on the tongue over less than one minute. |
Total time (seconds) crying over three minutes following heel lance
Time of first cry (seconds) following heel lance Per cent change in heart rate after heel lance (at 1 min, 3 min and 5 min) |
Analysis of non-parametric data was by the Mann-Whitney U test or a
trend test. Total time crying in the first three minutes after heel lance
was reported as medians and interquartile ranges. Changes in heart rate
were expressed in means and standard deviations as a percentage of resting
heart rate.
Adverse effects - were not evaluated |
B |
| Isik 2000a | Randomized controlled trial
I Blinding of randomization - can't tell II Blinding of intervention - can't tell III Complete follow-up - yes IV Blinding of outcome measurement - yes |
113 healthy newborns gestational ages between 37 and 42 weeks, median post natal age= 2days (range 2-5 days) | 2ml of 30% sucrose (n=28)
2ml of 10% glucose (n=29) 2ml of 30% glucose (n=28) 2ml of distilled water (n=28) syringed into the anterior third of the tongue for 1 minute 2 minutes prior to heel lance |
Mean cry time during 3 minutes after heel lance
Mean maximum heart rate 3 minutes from heel lance Mean recovery time for heart rate Percent change in heart rate at 1, 2, 3 minutes after heel lance |
One way ANOVA was used to evaluate mean cry time, recovery time and
% change in heart rate
Results reported as means and standard errors of the mean Adverse effects - were not evaluated |
B |
| Johnston 1997a | Randomized controlled trial
I Blinding of randomization - yes II Blinding of intervention - not for two interventions (rocking, and sucrose + rocking) III Complete follow-up - yes IV Blinding of outcome measurement - yes |
85 preterm infants (25 - 34 weeks gestational age) 2 - 10 days of age. | 0.05 ml of 24% sucrose via syringe into the mouth just prior to heel
lance (n = 27)
0.05 ml of 24% sucrose via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 14) 0.05 ml of sterile water via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 24) 0.05 ml of sterile water via syringe into the mouth just prior to heel lance |
Heart rate, oxygen saturation, behavioural facial actions, behavioural
state
(NFCS) baseline and at three 30 second blocks |
Data were analyzed using MANOVA (facial action). For heart rate repeated
measures ANOVA was used with mean values but no standard deviations presented
in graph form. For state repeated measures ANOVA was performed and no univariate
means and standard deviations were presented.
02 saturation was dropped from analysis Adverse effects - were not evaluated |
A |
| Johnston 1999a | Randomized controlled trial
I Blinding of randomization - yes II Blinding of intervention - yes III Complete follow-up - yes IV Blinding of outcome measurement - yes |
48 preterm neonates mean gestational age of 31 weeks (range 25-34 weeks) within 10 days of birth | 0.05ml of 24% sucrose as a single dose, followed by 2 doses of sterile
water (n=15)
3 doses of 0.05ml of 24% sucrose (n=17) 3 doses of 0.05ml of sterile water (n=16) given by syringe to anterior surface of the tongue at: 2 minutes prior to heel lance just prior to lancing 2 minutes after lancing |
Premature Infant Pain Profile
(PIPP) measured over five 30 second blocks of time |
Repeated measures ANOVA was used to evaluate the effect of single versus
repeated doses of sucrose.
Means and standard deviations for pain scores were obtained from the author Adverse effects - were not evaluated |
A |
| Ors 1999 | Randomized controlled trial
I Blinding of randomization - can't tell II Blinding of intervention -no III Complete follow-up - yes IV Blinding of outcome measurement - yes |
102 healthy term infants, gestational age 37-42 weeks, median postnatal age 1.6 days (range1-15 days) | 2ml of 25% sucrose (n=35)
2ml of human milk (n=33) 2ml of sterile water (n=34) syringed to anterior part of tongue for one minute Heel prick done 2 minutes after intervention |
Median crying time 3 minutes after heel lance
Percent change in heart rate 1, 2, 3 minutes after heel lance |
Kruskal-Wallis 1-way ANOVA used to assess differences between groups
Medians and interquartile ranges reported for outcomes Adverse effects - were not evaluated |
B |
| Overgaard 1999 | Double-blind randomized controlled trial
I Blinding of randomization - yes II Blinding of intervention - yes III Complete follow-up - yes IV Blinding of outcome measurement - yes |
100 newborn term infants [mean age 6 days (range 4-9)] | 2ml of 50% sucrose solution via syringe into the mouth over 30 seconds
2 minutes prior to heel lance
2ml of sterile water via syringe into the mouth over 30 seconds 2 minutes prior to heel lance |
NIPS
Crying time (duration of first cry, crying time during heel lance, fraction of crying during sampling, crying time during first minute after end of sampling, total crying time) NIPS one minute after heel lance and one minute after blood sampling Change in heart rate at 0,1 minutes Change in 02 saturation at 0,1 minutes |
Results were reported as medians and 5 and 95 percentiles
Statistical testing used Mann Whitney-U and Fisher's exact test Adverse effects: were not evaluated |
A |
| Ramenghi 1996a | Randomized, double blind, placebo controlled crossover study
I Blinding of randomization - can't tell II Blinding of intervention - yes III Complete follow-up - yes IV Blinding of outcome measurement - yes |
15 (32-34 weeks gestation) infants greater than 24 hours of age | 1 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance
1 ml of sterile water via syringe into mouth via syringe 2 minutes before heel lance. (n=15, cross over design) |
Duration of first cry (sec) following heel lance, percentage of time crying 5 minutes after heel lance, heart rate (at -2, 0, 1, 3, 5 min from heel lance), Behavioral scores (four facial expressions and the presence of cry (at -2, 0, 1, 3, 5 min from heel lance) | Medians and ranges were reported for duration of first cry, percent
cry over 5 minutes and heart rate. For composite behavioural outcome scores
data were presented in graph form only with no indication if data represent
medians or means. Wilcoxon matched pairs signed rank test used to evaluate
outcomes
Adverse effects - were evaluated |
B |
| Ramenghi 1996b | Randomized, single blind, placebo controlled trial
I Blinding of randomization - can't tell II Blinding of intervention - blind to all interventions except one (3/4). Calpol intervention not possible to blind due to pink colour of solution. III Complete follow-up - yes IV Blinding of outcome measurement - yes |
60 (37 - 42 weeks gestational age) 2 - 5 days old infants | 2 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance (n = 15).
2ml of 50% sucrose via syringe into mouth 2 minutes prior to heel lance (n =15). 2ml of commercial sweet tasting solution (Calpol) via syringe into mouth 2 minutes prior to heel lance (n = 15). 2ml of sterile water via syringe into mouth 2 minutes prior to heel lance (n = 15). |
Duration of first cry (sec) following heel lance, percent time crying over 3 minutes following heel lance, percent change in heart rate over 5 min (-2, 0, 1, 3, 5 min from heel lance), Behavioral scores (four facial expressions and the presence of cry (-2, 0, 1, 3, 5 min after heel lance) | Results were presented as medians and interquartile ranges for the
pain score. For cry duration and percent crying over three minutes the
data were presented as medians and inter quartile ranges. Percent change
in heart rate was reported in graph form without indicating if data represent
means or medians with standard deviations or errors. Mann-Whitney U test
used to evaluate outcomes
Adverse effects - were not evaluated |
B |
| Ramenghi 1999 | Randomized double blind placebo controlled cross over trial
I Blinding of randomization - can't tell II Blinding of intervention - can't tell. III Complete follow-up - yes IV Blinding of outcome measurement - can't tell |
30 preterm infants (GA 32-36 weeks, postnatal age < 24 hours) | 25 % sucrose solution (volume not reported) was given via syringe into
the mouth or via NG tube 2 minutes prior to first heel lance (n = 15),
and via the alternate route for the second heel lance within 48 hours
Sterile water via syringe into the mouth or via NG-tube 2 minutes prior to first heel lance and for the second heel lance the alternate route within 48 hours (cross over design, n= 30) |
Percentage cry over 5 minutes after sampling;
Behavioral scores (four facial expressions and the presence of cry) at 1, 3, and 5 minutes after the lance for a total behavioral score |
Mann Whitney-U and Wilcoxon matched pairs signed ranked test used to
evaluate outcomes
Results reported as median and interquartile and total range Adverse effects: were not evaluated |
B |
| Rushforth 1993 | Randomized, double blind, placebo controlled study
I Blinding of randomization - can't tell II Blinding of intervention - yes III Complete follow-up - yes IV Blinding of outcome measurement - yes |
52 infants (37 - 42 weeks gestational age) 2-7 days of age. | 2ml of 7.5% sucrose administered by a dropper into the mouth over a
one minute period prior to heel lance (n = 26).
2ml of sterile water administered by dropper into the mouth over a one minute period prior to heel lance (n = 26). |
Percentage time crying during sampling and 3 minutes following the completion of the heel lance recorded on a standard audio tape recorder and analysed blindly at a later date. | Results are presented as medians only with no ranges.
Mann Whitney-U test to evaluate duration of cry Adverse effects - were not evaluated |
B |
| Stevens 1999 | Randomized, cross-over
controlled trial I Blinding of randomization - can't tell II Blinding of intervention - no III Complete follow-up - yes IV Blinding of outcome measurement - yes |
122 neonates, 27 - 31 weeks gestational age, less than 28 days of age
Johnston, 1999b Subsample of 25 preterm neonates, 27-31 weeks gestational age, less than 28 days of age (refer to Stevens, 1999) |
Prone positioning 30 minutes prior to heel lance. Pacifier dipped in
sterile water and placed into the mouth 2 minutes prior to heel lance
Pacifier dipped in 24% sucrose and placed into the mouth 2 minutes prior to heel lance No treatment. (n = 122, crossover design) |
Premature Infant Pain Profile
(PIPP) |
Repeated measures ANOVA and ANCOVA used to evaluate efficacy of treatment
interventions
Means and standard deviations provided for pain scores Adverse effects - were evaluated |
B |
| Study | Reason for exclusion |
| Abad 1993 | Abstract |
| Abad 2001 | Although this is a randomized controlled trial, four newborns were included twice (i.e. there were 55 events recorded for 51 participants), therefore, it was not possible to separate data for 51 newborns. |
| Ahuja 2000 | This is a non-randomized study. A single cohort was studied. The intervention was a non-sucrose sweetener |
| Allen 1996 | Although this is a randomized double blind controlled trial it is not possible to determine the number of infants in the treatment and control groups. |
| Barr 1993 | Although a randomized controlled trial, the authors do not provide information on the number of infants in each group. Results are presented in graph form without indicating whether means or medians were used. No standard deviations are presented. |
| Blass 1991 | Although this is a randomized controlled trial the number of neonates in each group is not stated. |
| Blass 1995 | This is a controlled trial without randomization. The number of patients in each group is not stated |
| Bucher 2000 | This study used an artificial sweetner, glycine or breast milk as the intervention |
| Gibbins 2000 | Abstract |
| Gormally 1996 | Abstract |
| Graillon 1997 | A randomized controlled crossover study. 60 crying infants were randomized to receive 250 ul of 24% sucrose solution, 0.25% quinine hydrochloride solution, or corn oil as well as water in a mixed parallel crossover design. Relative to water, sucrose persistently reduced crying, and transiently increased mouthing and hand-mouth contact. No painful stimulus was applied to the neonates. |
| Herschel 1998 | The painful procedure in this study was circumcision |
| Isik 2000b | Abstract |
| Johnston 2000 | Abstract |
| Lewindon 1998 | The infants in this study were older than the inclusion criteria for this review (mean age 17.1 weeks). |
| Mellah 1999 | Randomized double blind cross-over study. Data analyzed by paired t-test. Results from the first exposure to sucrose or placebo could not be isolated. |
| Mohan 1998 | The painful procedure in this study was circumcision |
| Skogsdal 1997 | This study used glucose and breast milk as the interventions |
| Stang 1997 | The painful procedure in this study was circumcision |
| Stevens 1997b | Abstract |
| Stevens 2000 | Abstract |
Abad F, Diaz NM, Domenech E, Robayna M, Rico J. Oral sweet solution reduces pain-related behavior in preterm infants. Acta Paediatr 1996;85:854-8.
Blass 1999 {published data only}
Blass EM, Watt LB. Suckling- and sucrose-induced analgesia in human newborns. Pain 1999;82:1-13.
Bucher 1995 {published data only}
Bucher H-U, Moser T, von Siebenthal K, Keel M, Wolf M, Duc G. Sucrose reduces pain reaction to heel lancing in preterm infants: A placebo-controlled, randomized and masked study. Pediatr Res 1995;38:332-5.
Carbajal 1999 {published data only}
Carbajal R, Chauvet X, Couderc SD, Olivier-Martin M. Randomised trial of anagesic effects of sucrose, glucose, and pacifiers in term neonates. BMJ 1999;319:1393-1397.
Gibbins 2001 {published data only}
Gibbins SA. Efficacy and safety of sucrose for procedural pain relief in preterm and term neonates[dissertation] 2001.
Gormally 2001 {published data only}
Gormally S, Barr RG, Wertheim L, Alkawaf R, Calinoiu N, Young SN. Contact and nutrient caregiving effects on newborn infant pain responses. Develop Med Child Neurol 2001;43:28-38.
Haouari 1995 {published data only}
Haouari N, Wood C, Griffiths G, Levene M. The analgesic effect of sucrose in full term infants: a randomised controlled trial. BMJ 1995;310:1498-500.
Isik 2000a {published data only}
Isik U, Ozek E, Bilgen H, Cebeci D. Comparison of oral glucose and sucrose solutions on pain response in neonates. J Pain 2000;1(4):275-78.
Johnston 1997a {published data only}
Johnston C, Stremler R, Stevens B, Horton L, Stremler R. Effectiveness of oral sucrose and simulated rocking on pain response in preterm neonates. Pain 1997;72:193-9.
Johnston 1999a {published data only}
Johnston CC, Stremler R, Horton L, Friedman A. Effect of repeated doses of sucrose during heel stick procedure in preterm neonates. Biol Neonat 1999;75:160-66.
Ors 1999 {published data only}
Ors R, Ozek E, Baysoy G, Cebeci D, Bilgen H, Turkuner M, Basaran M. Comparison of sucrose and human milk on pain response in newborns. Eur J Pediatr 1999;158:63-66.
Overgaard 1999 {published data only}
Overgaard C, Knudesen A. Pain-relieving effect of sucrose in newborns during heel prick. Biol Neonate 1999;75:279-284.
Ramenghi 1996a {published data only}
Ramenghi LA, Wood CM, Griffith GC, Levene MI. Reduction of pain response in premature infants using intraoral sucrose. Arch Dis Child 1996;74:F126-128.
Ramenghi 1996b {published data only}
Ramenghi L, Griffith G, Wood C, Levene M. Effect of non-sucrose sweet tasting solution on neonatal heel prick responses. Arch Dis Child 1996;74:F129-31.
Ramenghi 1999 {published data only}
Ramenghi LA, Evans DJ, Levene MI. "Sucrose analgesia": absorptive mechanism or taste perception? Arch Dis Child Fetal Neonatal Ed 1999;80:F146-F147.
Rushforth 1993 {published data only}
Rushforth JA, Levene MI. Effect of sucrose on crying in response to heel stab. Arch Dis Child 1993;69:388-9.
Stevens 1999 {published data only}
* Stevens B, Johnston C, Franck P, et al. The efficacy of developmentally sensitive interventions and sucrose for relieving pain in very low birth weight infants. Nurs Res 1999;48:35-43.
Johnston CC, Sherrard A, Stevens B, Franck L, Stremler R, Jack A. Do cry features reflect pain intensity in preterm neonates? Biology of the Neonate 1999;76:120-24.
Abad F, Diaz NM, Domenech E, et al. Attentuation of pain related behavior in neonates given oral sweet solutions. Paris: 7th World Congress on Pain, 1993.
Abad 2001 {published data only}
Abad F, Diaz-Gomez NM, Domenech E, Gonzalez D, Robayna M, Feria M. Oral sucrose compares favourably with lidocaine-prilocaine cream for pain relief during venepuncture in neonates. Acta Paediatr 2001;90:160-5.
Ahuja 2000 {published data only}
Ahuja VK, Daga SR, Gosavi DV, Date AM. Non-sucrose sweetener for pain relief in sick newborns. Indian J Pediatr 2000;67:487-89.
Allen 1996 {published data only}
Allen K, White D, Walburn J. Sucrose as an analgesic agent for infants during immunization injections. Arch Pediatr Adolesc Med 1996;150:270-4.
Barr 1993 {published data only}
Barr RG, Oberlander T, Quek V, Brian J, Cassidy K-L, Beauparlant J, Young S. Dose-response analgesic effect of intraoral sucrose in newborns [abstract]. In: Prog Soc Res Child Develop. 1993.
Blass 1991 {published data only}
Blass EM, Hoffmeyer LB. Sucrose as an analgesic for newborn infants. Pediatrics 1991;87:215-8.
Blass 1995 {published data only}
Blass EM, Shah A. Pain-reducing properties of sucrose in human newborns. Chem Senses 1995;20:29-35.
Bucher 2000 {published data only}
Bucher HU, Baumgartner R, Bucher N, Seiler M, Fauchere JC. Artificial sweetner reduces nociceptive reaction in newborn infants. Early Hum Dev 2000;59:56-60.
Gibbins 2000 {published data only}
Gibbins S, Stevens B, Ohlsson A, Hodnett E, Pinelli J. Safety and efficacy of sucrose for procedural pain in neonates. In: The 5th International Symposium on Paediatric Pain. London, 2000:P98.
Gormally 1996 {published data only}
Gormally SM, Barr RG, Young SN, Alhawaf R, Wersheim L. Combined sucrose and carrying reduces newborn pain response more than sucrose or carrying alone. Arch Pediatr Adolesc Med 1996;150:47.
Graillon 1997 {published data only}
Graillon A, Barr RG, Young SN, Wright JH, Hendricks LA. Differential response to intraoral sucrose, quinine and corn oil in crying human newborns. Physiol Behav 1997;62:317-25.
Herschel 1998 {published data only}
Herschel M, Khoshnood B, Ellman C, Maydew N, Mittendorf R. Neonatal circumcision. Randomized trial of sucrose pacifier for pain control. Arch Pediatr Adolesc Med 1998;152:279-84.
Isik 2000b {published data only}
Isik U, Ozek E, Bilgen H, Ors R, Cebeci D, Basaran M. Comparison of oral dextrose and sucrose solutions on pain response in neonates. Pediatr Res 2000;47:403A.
Johnston 2000 {published data only}
Johnston C, Filion F, Majnemer A, et al. The efficacy of sucrose analgesia for procedural pain in preterm infants < 32 weeks in the first week of life. Pediatr Res 2000;47:405A.
Lewindon 1998 {published data only}
Lewindon PJ, Harkness L, Lewindon N. Randomized controlled trial of sucrose by mouth for the relief of infant crying after immunization. Arch Dis Child 1998;78:453-55.
Mellah 1999 {published data only}
Mellah D, Gourrier E, Merbouche S, Mouchino G, Crumiere C, Leraillez J.. Analgesie au saccharose lors des prelevements capillaires au talon. Etude randomisee chez 37 nouveau-nes de plus de 33 semaines d'amenorrhee [Analgesia with intraoral administration of saccharose during heel prick: a randomised, placebo controlled study in 37 newborn infants]. Arch Pediatr 1999;6:610-6.
Mohan 1998 {published data only}
Mohan CG, Risucci DA, Casimir M, Gulrajani-LaCorte M. Comparison of analgesics in ameliorating the pain of circumcision. J Perinatol 1998;18:13-9.
Skogsdal 1997 {published data only}
Skogsdal Y, Eriksson M, Schollin J. Analgesia in newborns given oral glucose. Acta Paediatrica 1997;86:217-20.
Stang 1997 {published data only}
Stang HJ, Snellman LW, Condon LM, Conroy MM, Liebo R, Brodersen L, Gunnar MR. Beyond dorsal penile nerve block: a more humane circumcision. Pediatrics 1997;100:E3.
Stevens 1997b {published data only}
Stevens B, Johnston C, Franck P, et al.. Nonpharmacologic interventions for decreasing procedural pain in preterm neonates. In: Fourth International Symposium on Pediatric Pain. Helsinki, 1997:154.
Stevens 2000 {published data only}
Stevens B, Petryshen P, Johnston C, Franck L, Jack A. The influence of consistent pain management on neonatal outcomes: preliminary findings. In: The 5th International Symposium on Paediatric Pain. London, UK, 2000:P96.
* indicates the primary reference for the study
American Academy of Pediatrics (the Committee on Fetus and Newborn; Committee on Drugs; Section on Anesthesiology; and Section on Surgery), Canadian Paediatric Society (the Fetus and Newborn Committee). Prevention and management of pain and stress in the newborn infant. Pediatrics 2000;105:454-461.
Anand KJS. Managing pain in newborns. How far have we really come? MD News Atlanta 1995;Oct/Nov:8-12.
Anand KJS, Abu-Saad HH, Aynsley-Green A, Bancalari E, Benini E, Champion GD, Craig KA, Dangel TS, Fournier-Charriere E, Franck LS, Eckstein Grunau R, Hertel SA, Jacqz-Aigrain E, Jorch G, Kopelman BI, Koren G, Larsson B, Marlow N, McIntosh N, Ohlsson A, Porter F, Richter R, Stevens B, Taddio A. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 2001;153:173-80.
Barr RG, Quek V, Cousineau D, Oberlander T, Brian J, Young S. Effects of intraoral sucrose on crying, mouthing and hand-mouth contact in newborn and six-week old infants. Dev Med Child Neurol 1994;36:608-18.
Campos RG. Rocking and pacifier; two comforting interventions for heel stick pain. Res Nurs Health 1994;17:321-31.
DiPietro JA, Cusson RM, O'Brian CM, et al. Behavoural and physiological effects of nonnutritive sucking during gavage feeding in preterm infants. Pediatr Res 1994;36:207-14.
Fernandes CV, Rees EP. Pain management in Canadian level 3 neonatal intensive care units. Can Med Assoc J 1994;150:469-70.
Gunnar MR, Connors J, Isensee J, Wall L. Adrenocortical activity and behavioral distress in human newborns. Dev Psychobiol 1988;21:297-310.
Gunnar MR. Reactivity of the hypothalamic-pituitary-adrenocortical system to stressors in normal infants and children. Pediatrics 1992;90:491-7.
Haynes MJ, Smith BA, Herrick S, et al. Behavioural differences between term and postmature infants in sucrose calming test [abstract]. Prog Soc Res Child Develop 1995.
Johnston CC, Collinge JM, Henderson SJ, Anand KJ. A cross-sectional survey of pain and pharmacological analgesia in Canadian neonatal intensive care units. Clin J Pain 1997;13:308-12.
Ohlsson A. Prevention and management of pain and stress in the newborn infant. Paediatr Child Health 2000;5:31-47.
Smith BA, Stevens K, Torgerson WS, et al. Diminished reactivity of postmature human infants to sucrose compared with term infants. Dev Psychol 1992;29:811-20.
Stevens B, Johnston C, Horton L. Factors that influence the behavioral responses of premature infants. Pain 1994;59:101-9.
Stevens B, Johnston C, Petryshen P, Taddio A. Premature infants pain profile: developmental and initial validation. Clin J Pain 1996;12:13-22.
Stevens B, Taddio A, Ohlsson A, Einarson T. The efficacy of sucrose for relieving procedural pain in neonates - a systematic review and meta-analysis. Acta Paediatr 1997;86:837-42.
Stevens B. Composite measures of pain in children. In: Finley GA, McGrath PJ, editor(s). Measurement of pain in infants and children. Progress in Pain Research and Management. Vol. 10. Seattle: IASP Press, 1997:161-77.
Stevens B, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. In: The Cochrane Library, Issue 1, 1998. Oxford: Update Software.
Walia R, Ohlsson A. Clinical trials in neonatal medicine. In: 7th Annual Cochrane Colloquium, Abstracts, October 1999. Rome, 1999.
Willis D, Chabot J, Radde I, Chance G. Unsuspected hyperosmolality of oral solutions contributing to necrotizing enterocolitis in very-low-birth-weight infants. Pediatrics 1977;60:535-8.
02 Sucrose 25 - 30 % vs. Control (Sterile water)
02.01 % change in heart rate 1 minute
after heel lance
02.02 % change in heart rate 3 minutes
after heel lance
| Study | Participants | Procedure | Intervention | Outcomes | Metrics used | Results |
| Abad 1996 | 28 preterm (29 - 36 weeks gestational age) infants, postnatal age 1-26 days | Venepuncture | 2ml of 12% sucrose via syringe (n = 8)
2ml of 24% sucrose via syringe (n = 8) 2ml of spring water via syringe (n = 12) 2 minutes prior to venepuncture |
Time crying for 3 minutes after venepuncture | Median, IQR | Cry duration for 3 minutes after venepuncture was significantly reduced in 2ml of 24% (0.48 g) sucrose group, p <0.05 (19.1 sec), but not in 2ml of 12% (.24g) sucrose group (63.1 sec) compared to water (72.9 sec). Significant group effect noted, F (2, 25) = 4.26; p = 0.0256 |
| Blass 1999 | 40 term newborn infants, 34 - 55 hours old | Heel Lance | 2ml of 12% sucrose over 2 minutes via syringe (n=10)
2ml of water via syringe over 2 minutes (n=10) Pacifier dipped every 30 seconds in 12% sucrose solution for 2 minutes (n=10) Pacifier dipped in water every 30 seconds for 2 minutes (n = 10) prior to heel lance |
% time crying 3 minutes after heel lance | Not reported | 2ml of 12% (0.24g) sucrose alone diminished cry duration from heel lance compared to water ( 8% vs. 50%, p = 0.003) and water with pacifier ( 8% vs. 35%, p = 0.002). Sucrose with pacifier (pacifier with 12% sucrose) more effective in reducing cry duration compared to water with pacifier (5% vs. 35%, p = 0.001) or water alone (50%, p = 0.002) |
| Bucher 1995 | 16 preterm infants (27 - 34 weeks gestational age), postnatal age approximately 42 days | Heel Lance | 2ml of 50% sucrose via syringe into the mouth 2 minutes before heel
lance.
2ml of distilled water via syringe into the mouth 2 minutes before heel lance (n = 16, cross-over design) |
% time crying
Recovery time until crying stopped |
Not reported | Cry duration (% of total duration of intervention) significantly reduced in 2ml of 50% (1.0 g) sucrose group (71.5%) compared to control group (93.5%), p = 0.002 |
| Gormally 2001 | 94 term newborns, mean gestational age 39.4 weeks on 2nd or 3rd day of life | Heel Lance | No holding and sterile water given by pipette (n=21)
No holding and 0.250 ml of 24% sucrose solution given by pipette (n=22) Holding and sterile water given by pipette (n=20) Holding and 0.250 ml of 24% sucrose solution by pipette (n=22) All solutions given 3 times at 30 second intervals |
% time crying 1, 2, 3 minutes after heel lance | Not reported | Crying decreased over time [F(2,80) = 10.0, p<0.001] but no significant interaction noted for time with holding, taste, or holding and taste. Effect of taste on crying was significant [F(1,81) = 4.1, p<0.05] in favour of 0.250ml of 24% (0.18g) sucrose. Effect of holding not statistically significant [F(1,81) = 3.0, p = 0.09)]. No statistically significant interaction between taste and holding to reduce crying [F(1,81) = 0.80, p = 0.37]. Effect of combined interventions was additive |
| Haouari 1995 | 60 term (37-42 weeks gestation) infants. 1-6 days of age | Heel Lance | 2ml of 12.5% sucrose 2 minutes prior to heel lance (n = 15)
2 ml of 25% sucrose 2 minutes prior to heel lance (n = 15). 2 ml of 50 % sucrose 2 minutes prior to heel lance (n = 15). 2ml of sterile water 2 minutes prior to heel lance (n = 15). All solutions were given by syringe on the tongue over less than one minute |
Total time crying over 3 minutes. Time of first cry after lance | Median, IQR | After heel lance, significant decreases in total crying time and duration of first cry in 2ml of 50% (1.0 g) sucrose group compared with water (p = 0.02). Significant reduction in median time crying at end of first minute (p <0.02) in 2ml of 50%(1.0 g) sucrose group (35 sec; range 14 - 60) compared with water (60 sec; range 50 -60). In second minute, duration of cry was significantly less in 2ml of 50%(1.0 g) sucrose group (0 sec; range 0 - 25) and in 2ml of 25%(0.5 g) sucrose group (18 sec; range 0 - 55) compared to water (60 sec; range 40 - 60), p = 0.003, p = 0.02 respectively |
| Isik 2000 | 113 healthy term newborns gestational ages between 37 and 42 weeks, median post natal age= 2days (range 2-5 days) | Heel Lance | 2ml of 30% sucrose (n=28)
2ml of 10% glucose (n=29) 2ml of 30% glucose (n=28) 2ml of distilled water (n=28) syringed into the anterior third of the tongue for 1 minute 2 minutes prior to heel lance |
Mean cry time during 3 minutes after lance | Reported means, SD | Infants who received 2ml of 30% (0.6g) sucrose (mean crying time of 61 seconds) cried significantly less than those who received 30% glucose (mean crying time of 95 seconds), 10% glucose (mean crying time of 103 seconds) or sterile water (mean crying time of 105 seconds), p = 0.02 |
| Ors 1999 | 102 healthy term infants, gestational age 37-42 weeks, median postnatal age 1.6 days (range1-15 days) | Heel Lance | 2ml of 25% sucrose (n=35)
2ml of human milk (n=33) 2ml of sterile water (n=34) syringed to anterior part of tongue for one minute Heel prick done 2 minutes after intervention |
Median cry time during 3 minutes after lance | Median, IQR | Significant decrease in crying times for 2ml of 25% (0.5 g) sucrose group (median 36, interquartile range 18-43) compared to human milk (median 62, interquartile range 29-107) and sterile water [(median 52, interquartile range 32-158), p = 0.0009]. Recovery time for crying was significantly reduced in 2ml of 25% (0.5g )sucrose group (median 72, interquartile range 48-116) compared to human milk (median 112, interquartile range 72-180) and sterile water [(median 124, interquartile range 82-180), p = 0.004] |
| Overgaard 1999 | 100 newborn term infants [mean age 6 days (range 4-9)] | Heel Lance | 2ml of 50% sucrose solution via syringe into the mouth over 30 seconds
2 minutes prior to heel lance
2ml of sterile water via syringe into the mouth over 30 seconds 2 minutes prior to heel lance |
Median crying time during heel lance, fraction of crying during sampling, crying time during first minute after end of sampling, total crying time | Median, 5th and 95th percentiles | Median duration of first cry in group receiving 2ml of 50%(1g) sucrose was significantly lower (18 seconds (2-75) compared to placebo group [(22 seconds (11-143), p = 0.03]. Median crying time during heel lance in the sucrose group was lower (26 seconds (2-183) compared to placebo group [(40 seconds (12 - 157), p = 0.07]. Median fraction of crying during sampling in 2ml of 50% (1g) sucrose group was significantly lower (43% (4-100) compared to placebo group [(83% (20 - 100), p = 0.004]. Median crying time during first minute after end of sampling in 2ml of 50% (1g) sucrose group was significantly lower (3 seconds (0-58) compared to placebo group [(16 seconds (0-59), p=0.004]. Median total time crying in 2ml of 50% (1g) sucrose group was significantly lower (30 seconds (2-217) compared to placebo group [(71 seconds (13-176), p = 0.007] |
| Ramenghi 1996a | 15 preterm(32-34 weeks gestation) infants greater than 24 hours of age | Heel Lance | 1 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance
1 ml of sterile water via syringe into mouth via syringe 2 minutes before heel lance. (n=15, cross-over design) |
Duration of first cry and
% time crying 5 minutes after lance |
Median, IQR | Significant decrease in total percentage of time crying over 5 minutes (median 6%, interquartile range 3.3 - 15.3) in the 1ml of 25% (0.25 g) sucrose group compared with water group [(median 16.6%, range 5 - 27.3), p = 0.018]. Duration of first cry was significantly decreased in the 1ml of 25% (0.25g) sucrose group (median 12 sec, interquartile range 8 - 22 sec) compared to control group [(median quartile 23 sec, range 15 - 45), p = 0.004] |
| Ramenghi 1996b | 60 term (37 - 42 weeks gestational age) 2 - 5 days old infants | Heel Lance | 2 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance (n = 15).
2ml of 50% sucrose via syringe into mouth 2 minutes prior to heel lance (n =15). 2ml of commercial sweet tasting solution (Calpol) via syringe into mouth 2 minutes prior to heel lance (n = 15). 2ml of sterile water via syringe into mouth 2 minutes prior to heel lance (n = 15). |
Duration of first cry after lance
% time crying over 3 minutes after heel lance |
Median, IQR | Significant decrease in duration of first cry and percent crying during 3 minutes after heel lance in the 2ml of 25% (0.5 g) sucrose, 2ml of 50% (1.0 g) sucrose and Calpol groups (p = 0.02) (data in graph form only) |
| Ramenghi 1999 | 30 preterm infants (GA 32-36 weeks, postnatal age < 24 hours) | Heel Lance | 25 % sucrose solution (volume not reported) was given via syringe into
the mouth or via NG tube 2 minutes prior to first heel lance (n = 15),
and via the alternate route for the second heel lance within 48 hours
Sterile water via syringe into the mouth or via NG-tube 2 minutes prior to first heel lance and for the second heel lance the alternate route within 48 hours (cross over design, n= 30) |
% cry over 5 minutes after sampling | Median, IQR | Median percentage cry in intraoral water group was 22% (interquartile range 10.6 - 40) and 27% (interquartile range 11.6 - 47) for infants in NG-tube water group. Median percentage cry in intraoral 25% sucrose group was 6% (interquartile range 0.6-15) and 18.3% (interquartile range 11.6-41.6) for NG-tube 25% sucrose group. Significant reduction in crying time (p = 0.006) noted in the 25% sucrose group compared with water group when infants received 25% sucrose intraorally, not via NG-tube route. For infants in 25% sucrose group, significant reduction in crying time noted (p = 0.008) when solution given intraorally compared to NG-tube route |
| Rushforth 1993 | 52 term infants (37 - 42 weeks gestational age) 2-7 days of age. | Heel Lance | 2ml of 7.5% sucrose administered by a dropper into the mouth over a
one minute period prior to heel lance (n = 26).
2ml of sterile water administered by dropper into the mouth over a one minute period prior to heel lance (n = 26 |
% cry over 3 minutes after sampling | Median only | No significant differences in median percentage time crying between group receiving 2ml of 7.5% (0.15g) sucrose (74.3%) compared to group receiving water (73.2%). No significant differences between groups in duration of cry after 1 minute (p = 0.65), 2 minutes (p = 0.52) and 3 minutes (p = 0.72). No difference in time to cessation of crying (p = 0.16) |
| Study | Participants | Procedure | Interventions | Outcomes | Metrics used | Results |
| Abad 1996 | 28 preterm (29 - 36 weeks gestational age) infants, postnatal age 1-26 days | Venepuncture | 2ml of 12% sucrose via syringe (n = 8)
2ml of 24% sucrose via syringe (n = 8) 2ml of spring water via syringe (n = 12) 2 minutes prior to venepuncture |
Heart rate:
pre solution, post solution 5 minutes after venepuncture |
Reported means and SEM | Significant group effect, F (2, 25) = 6.37, p = 0.006 Overall time effect, F (2, 50) = 14.15, p < 0.001 No significant interaction between treatment group and time. Post hoc Tukey test showed that group receiving 2 ml of 12% sucrose (0.24g) had lower HR compared to the 2ml of 24% sucrose group (0.48g) or water group |
| Blass 1999 | 40 term newborn infants, 34 - 55 hours old | Heel lance | 2ml of 12% sucrose over 2 minutes via syringe (n=10)
2ml of water via syringe over 2 minutes (n=10) Pacifier dipped every 30 seconds in 12% sucrose solution for 2 minutes (n=10) Pacifier dipped in water every 30 seconds for 2 minutes (n = 10) prior to heel lance |
Change in mean HR | Not reported | Mean heart rate increased significantly from treatment to heel lance in infants receiving water alone (mean increase of 17 beats per minute, p = 0.002) and water with pacifier (mean increase of 20 beats per minute, p = 0.005). Mean increase in heart rates also increased for the 2ml of 12% (.24g) sucrose and pacifier group (mean difference of 7.4 beats per minute, p = 0.05) but not for infants receiving 2ml of 12%(0.24g) sucrose alone (mean difference of 5.9 beats per minute, p = 0.142) |
| Bucher 1995 | 16 preterm infants (27 - 34 weeks gestational age), postnatal age approximately 42 days | Heel lance | 2ml of 50% sucrose via syringe into the mouth 2 minutes before heel
lance.
2ml of distilled water via syringe into the mouth 2 minutes before heel lance (n = 16, cross-over design) |
Increase in HR
Recovery time for HR |
Median, IQR | Median increase in heart rate [beats per minute (bpm)] after heel lance were significantly reduced in the 2ml of 50%(1.0 g) of sucrose group (35 bpm) compared to water (51 bpm), p = 0.005 |
| Gormally 2001 | 94 term newborns, mean gestational age 39.4 weeks on 2nd or 3rd day of life | Heel lance | No holding and sterile water given by pipette (n=21)
No holding and 0.250 ml of 24% sucrose solution (0.06g) given by pipette (n=22) Holding and sterile water given by pipette (n=20) Holding and 0.250 ml of 24% sucrose solution (0.06 g) by pipette (n=22) All solutions given 3 times at 30 second intervals |
Mean HR preintervention, 1, 2, 3 minutes after heel lance, Mean vagal tone index preintervention, 1, 2, 3 minutes after heel lance | Not reported for both HR and vagal tone | Although no significant differences in mean heart rate due to holding or sucrose as main effects, there was significant interaction between holding and taste [F(1,61) = 8.89, p<0.004], indicating synergistic effect that was also dependent on preintervention heart rate [F(1,61) = 9.23, p<0.004]. No significant main effects noted for vagal tone; as with heart rate, effect of vagal tone was dependent on preintervention vagal tone for both holding and taste interventions [F(1,60) = 4.82, p<0.03]. Preintervention levels interacted to decrease heart rate and vagal tone in infants who had higher rates before interventions |
| Haouari 1995 | 60 term (37-42 weeks gestation) infants. 1-6 days of age | Heel lance | 2ml of 12.5% sucrose 2 minutes prior to heel lance (n = 15)
2 ml of 25% sucrose 2 minutes prior to heel lance (n = 15). 2 ml of 50 % sucrose 2 minutes prior to heel lance (n = 15). 2ml of sterile water 2 minutes prior to heel lance (n = 15). All solutions were given by syringe on the tongue over less than one minute |
Percent change in HR at 1, 3, 5 minutes after heel lance | Reported Means and SEM | Significant decrease in percent change in heart rate 3 minutes after heel lancing (p = 0.02) in the 2ml of 50% (1.0 g) sucrose group (mean 0.1%, SE 3.3) compared to water group (mean 17.5%, SE 6.0) |
| Isik 2000 | 113 healthy term newborns gestational ages between 37 and 42 weeks, median post natal age= 2days (range 2-5 days) | Heel lance | 2ml of 30% sucrose (n=28)
2ml of 10% glucose (n=29) 2ml of 30% glucose (n=28) 2ml of distilled water (n=28) syringed into the anterior third of the tongue for 1 minute 2 minutes prior to heel lance |
Mean maximum heart rate 3 minutes from heel lance
Mean recovery time for heart rate % change in heart rate at 1, 2, 3 minutes after heel lance |
Reported Means and SEM | No significant difference between groups with respect to maximum heart rate after heel lance, (p = 0.71), or mean recovery time,(p = 0.09). No significant difference found in percent change in heart rate at 1 or 3 minutes after heel lance, (p = 0.14, p = 0.53), respectively. At 2 minutes after heel lance, percent change in heart rate favoured group receiving sucrose (p = 0.05) compared to other groups |
| Johnston 1997a | 85 preterm infants (25 - 34 weeks gestational age) 2 - 10 days of age | Heel lance | 0.05 ml of 24% sucrose via syringe into the mouth just prior to heel
lance (n = 27)
0.05 ml of 24% sucrose via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 14) 0.05 ml of sterile water via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 24) 0.05 ml of sterile water via syringe into the mouth just prior to heel lance |
HR at baseline and 3 x 30 second blocks | Not reported | Although heart rate increased across all phases of procedure [F(3,59) = 2.94, p <0.04], there was no significant differences noted between groups [F(3,59)=0.682, p = 0.566] |
| Ors 1999 | 102 healthy term infants, gestational age 37-42 weeks, median postnatal age 1.6 days(range1-15 days) | Heel lance | 2ml of 25% sucrose (n=35)
2ml of human milk (n=33) 2ml of sterile water (n=34) syringed to anterior part of tongue for one minute Heel prick done 2 minutes after intervention |
Percent change HR 1,2,3 minutes after heel lance | Median, IQR | Percent change in heart rate after heel lance was significantly lower in the group receiving 2ml of 25%(.5g) sucrose compared to groups receiving human milk and sterile water at 1, 2 and 3 minutes (p = 0.008, p = 0.01, p = 0.002, respectively) |
| Overgaard 1999 | 100 newborn term infants [mean age 6 days (range 4-9)] | Heel lance | 2ml of 50% sucrose solution via syringe into the mouth over 30 seconds
2 minutes prior to heel lance
2ml of sterile water via syringe into the mouth over 30 seconds 2 minutes prior to heel lance |
Change HR 0,1 minutes | Median, 5th and 95th percentiles | No significant differences between groups, p = 0.05 |
| Ramenghi 1996a | 15 preterm (32-34 weeks gestation) infants greater than 24 hours of age | Heel lance | 1 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance
1 ml of sterile water via syringe into mouth via syringe 2 minutes before heel lance. (n=15, cross over design) |
Heart rate (at -2, 0, 1,3,5 minutes from heel lance) | Median, IQR | No significant differences between groups, p-value not reported |
| Ramenghi 1996b | 60 term (37 - 42 weeks gestational age) 2 - 5 days old infants | Heel lance | 2 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance (n = 15).
2ml of 50% sucrose via syringe into mouth 2 minutes prior to heel lance (n =15). 2ml of commercial sweet tasting solution (Calpol) via syringe into mouth 2 minutes prior to heel lance (n = 15). 2ml of sterile water via syringe into mouth 2 minutes prior to heel lance (n = 15). |
Percent change in heart rate over 5 minutes (at -2, 0, 1,3,5 minutes from heel lance) | Not reported | Significant increase in heart rate for 3 minutes after heel lance in water group compared with 2ml of 50% (1.0 g) sucrose group and Calpol group, p = 0.009 |
| Study | Participants | Procedure | Interventions | Outcomes | Metrics used | Results |
| Abad 1996 | 28 preterm (29 - 36 weeks gestational age) infants, postnatal age 1-26 days | Venepuncture | 2ml of 12% sucrose via syringe (n = 8)
2ml of 24% sucrose via syringe (n = 8) 2ml of spring water via syringe (n = 12) 2 minutes prior to venepuncture |
Mean 02saturation and respiratory rate pre solution, post solution, 5 minutes after venepuncture | Reported means, SD | No significant differences noted between groups over time for oxygen saturation and respiratory rates (no p-values reported ) |
| Bucher 1995 | 16 preterm infants (27 - 34 weeks gestational age), postnatal age approximately 42 days | Heel Lance | 2ml of 50% sucrose via syringe into the mouth 2 minutes before heel
lance.
2ml of distilled water via syringe into the mouth 2 minutes before heel lance (n = 16, cross-over design) |
tcpO2 (max increase -kPa); tcpO2 (max decrease -kPa); tcpO2 (difference between baseline and 10 minutes after end of intervention -kPa); tcpCO2 (max decrease -kPa); tcpCO2 (difference between baseline and 10 min after the end of intervention), recovery time for respirations. | Median, IQR | No significant differences between groups with respect to measures for tcP02( p = 0.05) and tcPC02(p = 0.21) |
| Johnston 1997a | 85 preterm infants (25 - 34 weeks gestational age) 2 - 10 days of age | Heel Lance | 0.05 ml of 24% sucrose via syringe into the mouth just prior to heel
lance (n = 27)
0.05 ml of 24% sucrose via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 14) 0.05 ml of sterile water via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 24) 0.05 ml of sterile water via syringe into the mouth just prior to heel lance |
02 saturation | Not reported | 02 saturation dropped from analysis |
| Overgaard 1999 | 100 newborn term infants [mean age 6 days (range 4-9)] | Heel Lance | 2ml of 50% sucrose solution via syringe into the mouth over 30 seconds
2 minutes prior to heel lance
2ml of sterile water via syringe into the mouth over 30 seconds 2 minutes prior to heel lance |
02 saturation at 0, 1 minutes | Median, 5th and 95th percentiles | No significant differences between groups with respect to changes in oxygen saturation, p = 0.8 |
| Study | Participants | Procedure | Interventions | Outcomes | Metrics used | Results |
| Ramenghi 1996a | 15 (32-34 weeks gestation) infants greater than 24 hours of age | Heel Lance | 1 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance
1 ml of sterile water via syringe into mouth via syringe 2 minutes before heel lance. (n=15, cross-over design) |
Quality/intensity of sucking | Not reported | The clinical interpretation of the quality of sucking was significantly more intense in the 1ml of 25%(0.25 g) sucrose group than in the water group (p=0.04). |
| Study | Participants | Procedure | Intervention | Outcomes | Metrics used | Results |
| Blass 1999 | 40 term newborn infants, 34 - 55 hours old | Heel Lance | 2ml of 12% sucrose over two minutes via syringe (n=10)
2ml of water via syringe over 2 minutes (n=10) Pacifier dipped every 30 seconds in 12% sucrose solution for two minutes (n=10) Pacifier dipped in water every 30 seconds for two minutes (n = 10) prior to heel lance |
% time grimacing | Not reported | 2ml of 12%(0.24g) sucrose reduced grimacing compared to water, p = 0.0003 12%(0.24g) sucrose with pacifier reduced grimacing compared to water, p = 0.002 and water with pacifier, p = 0.04 |
| Study | Participants | Procedure | Interventions | Outcomes | Metrics used | Results |
| Carbajal 1999 | 150 term newborn infants, 3-4 days old | Venepuncture | No treatment (n = 25)
2 ml of sterile water via syringe over 30 seconds (n = 25) 2 ml of 30% glucose via syringe (n = 25) 2 ml of 30% sucrose (n = 25) Pacifier alone (n = 25) 2 minutes prior to venepuncture 2 ml of 30% sucrose via syringe followed by sucking a pacifier (n = 25 |
Douleur Aigue du Nouveau-ne (DAN) scale | Median, IQR | Median pain scores with interquartile ranges during venepuncture were: No treatment 7 (5-10); sterile water group 7 (6-10); 30% glucose group 5 (3-7); 2ml of 30% sucrose (0.6g) group 5 (2-8); pacifier alone group 2 (1-4); 2ml of 30% (0.6g) sucrose with pacifier group 1 (1-2). All groups had significantly lower pain scores compared to sterile water group: 30% glucose (p = 0.005), 2ml of 30% (0.6g) sucrose (p = 0.01), pacifier (p <0.0001), 2ml of 30% (0.6g) sucrose with pacifer (p <0.0001). Pacifier alone group had significantly lower pain scores than infants receiving 30% glucose (p = 0.0001) or 2ml of 30% (0.6g) sucrose (p = 0.001). Trend towards lower pain scores for infants receiving 2ml of 30% (0.16g) sucrose with pacifier compared to pacifier alone (p <0.06) |
| Gormally 2001 | 94 term newborns, mean gestational age 39.4 weeks on 2nd or 3rd day of life | Heel Lance | No holding and sterile water given by pipette (n=21)
No holding and 0.250 ml of 24% sucrose solution given by pipette (n=22) Holding and sterile water given by pipette (n=20) Holding and 0.250 ml of 24% sucrose solution by pipette (n=22) All solutions given 3 times at 30 second intervals |
Pain concatenation scores for facial activity
preintervention, 1, 2, 3 minutes after heel lance |
Not reported | Pain concatenation scores measuring facial expressions of pain decreased over time [F(1,65) = 28.5, p<0.001]. Only the effect of holding reduced pain scores [F(1,65) = 5.6, p<0.02].No difference as to whether infant received sucrose (taste main effect F[1,65] 0.17,p=0.68 |
| Johnston 1997a | 85 preterm infants (25 - 34 weeks gestational age) 2 - 10 days of age | Heel Lance | 0.05 ml of 24% sucrose via syringe into the mouth just prior to heel
lance (n = 27)
0.05 ml of 24% sucrose via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 14) 0.05 ml of sterile water via syringe into the mouth just prior to heel lance and simulated rocking 15 minutes prior to heel lance (n = 24) 0.05 ml of sterile water via syringe into the mouth just prior to heel lance |
Behavioural facial actions(Neonatal Facial Coding System-NFCS) at baseline and 3 x30 second blocks | Not reported | Decrease in percent facial action in 0.05ml of 24% (0.012g) sucrose alone group and combined 0.05ml of 24%(0.012g) sucrose and rocking group compared to water group, F (6, 150) = 2.765, p < 0.02 |
| Ramenghi 1996a | 15 (32-34 weeks gestation) infants greater than 24 hours of age | Heel Lance | 1 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance
1 ml of sterile water via syringe into mouth via syringe 2 minutes before heel lance. (n=15, cross-over design) |
Behavioral scores (four facial expressions and the presence of cry) -2,-1,0,1,2,3,5 minutes | Not reported | Mean pain scores were significantly lower in the groups receiving 1ml of 25% sucrose(0.25g )of sucrose at both 1 minute and 3 minutes after heel lance ( p = 0.01, p = 0.03, respectively) |
| Ramenghi 1996b | 60 term (37 - 42 weeks gestational age) 2 - 5 days old infants | Heel Lance | 2 ml of 25% sucrose via syringe into mouth 2 minutes prior to heel
lance (n = 15).
2ml of 50% sucrose via syringe into mouth 2 minutes prior to heel lance (n =15). 2ml of commercial sweet tasting solution (Calpol) via syringe into mouth 2 minutes prior to heel lance (n = 15). 2ml of sterile water via syringe into mouth 2 minutes prior to heel lance (n = 15). |
Behavioral scores (four facial expressions and the presence of cry) -2,-1,0,1,2,3,5 minutes | Median, IQR | Pain score (0 - 5) was significantly higher in water group (score = 2, range 1-5) than in other three groups [(2ml of 50%(1 g )sucrose group score = 0, range 0 - 3; 2ml of 25%(0.5 g) sucrose group score = 0, range 0 - 2; Calpol group score = 0, range 0 -1), p = 0.05 |
| Ramenghi 1999 | 30 preterm infants (GA 32-36 weeks, postnatal age < 24 hours) | Heel Lance | 25 % sucrose solution (volume not reported) was given via syringe into
the mouth or via NG tube 2 minutes prior to first heel lance (n = 15),
and via the alternate route for the second heel lance within 48 hours
Sterile water via syringe into the mouth or via NG-tube 2 minutes prior to first heel lance and for the second heel lance the alternate route within 48 hours (cross over design, n= 30) |
Behavioral scores (four facial expressions and the presence of cry) at 1, 3, and 5 minutes after the lance for a total behavioral score | Median, IQR | Behavioral scores for the intraoral water group was 9 (interquartile range 6-12) and 10 (interquartile range 6-14) for N-G tube water group. Behavioural scores for intraoral 25% sucrose group was 5 (interquartile range 3-6) and 9 (interquartile range 8-10) for NG-tube sucrose group. Significant reduction in behavioral scores noted in 25% sucrose group (p = 0.002) compared with water group when infants received 25% sucrose intraorally but not via N-G route. For infants in 25% sucrose group, there was significant reduction in behavioral score, p = 0.001 when solution was given intraorally compared to via NG-tube |
| Study | Participants | Procedure | Interventions | Outcomes | Metrics used | Results |
| Gibbins 2001 | 190 preterm and term infants , mean gestational age of 33.7 weeks, under 7 days post natal age | Heel Lance | 0.5ml of 24% sucrose via syringe to the anterior surface of the tongue
followed by pacifier (n=64)
0.5ml 24% sucrose without pacifier (n=62) 0.5ml sterile water with pacifier (n=64) 2 minutes prior to heel lance |
Premature Infant Pain Profile (PIPP) scores at 30 and 60 seconds after heel lance | Reported Means, SD | Statistically significant difference in mean PIPP scores at both 30 seconds (F = 8.23, p<0.001) and 60 seconds (F = 8.49, p<0.001) after heel lance in favour of 0.5ml of 24%(0.12g) sucrose group and 0.5ml of 24%(0.12g) sucrose with pacifier group. Post-hoc Tukey tests showed infants who received sucrose and pacifier had significantly lower PIPP scores after heel lance at 30 seconds (mean 8.16, SD 3.24) compared to infants receiving sucrose alone (mean 9.77, SD 3.04, p = 0.007) and water with pacifier (mean 10.19, SD 2.67, p<0.001). At 60 seconds after heel lance, PIPP scores were significantly lower for 0.5ml of 24%(0.12g) sucrose with pacifier group (mean 8.78, SD 4.03) compared to the 0.5ml of 24%(0.12g)sucrose alone group (mean 11.20, SD 3.25, p = 0.005) and water with pacifier group (mean 11.20, SD 3.47, p = 0.007). No significant differences in PIPP scores found between 0.5ml 0f 24%(0.12g) sucrose alone group or water with pacifier group at both follow-up times |
| Johnston 1999a | 48 preterm neonates mean gestational age of 31 weeks (range 25-34 weeks) within 10 days of birth | Heel Lance | 0.05ml of 24% sucrose as a single dose, followed by 2 doses of sterile
water (n=15)
3 doses of 0.05ml of 24% sucrose (n=17) 3 doses of 0.05ml of sterile water (n=16) given by syringe to anterior surface of the tongue at: 2 minutes prior to heel lance just prior to lancing 2 minutes after lancing |
Premature Infant Pain Profile( PIPP) scores in five 30 second blocks | Reported Means, SD | Statistically significant difference between groups (F = 9.143, p<0.0001) for mean PIPP scores. Post-hoc analysis found significantly lower PIPP scores with repeated doses of 0.05ml of 24%(0.012g) sucrose compared to placebo groups across all blocks of time, p<0.05. PIPP scores for repeated doses of 0.05ml of 24%(0.012g) sucrose were significantly lower compared to single doses of 0.05ml of 24%(0.012g)sucrose (8.25 vs. 6.25) only at last block of time, p<0.05. PIPP scores for single doses of 0.05ml of 24%(0.012g) sucrose compared to placebo showed trend towards statistical significance in favour of 0.05ml of 24%(0.012g)sucrose (F = 3.465, p = 0.07) |
| Overgaard 1999 | 100 newborn term infants [mean age 6 days (range 4-9)] | Heel Lance | 2ml of 50% sucrose solution via syringe into the mouth over 30 seconds
2 minutes prior to heel lance
2ml of sterile water via syringe into the mouth over 30 seconds 2 minutes prior to heel lance |
NIPS scores 1 minute after heel lance and 1 minute after blood sampling | Median, 5th and 95th percentiles | Median NIPS scores 1 minute after heel lance were lower in 2ml of 50% (1.0 g) sucrose group compared to placebo group [(3(0-7), 6(0-7), respectively), p = 0.04]. Median NIPS scores 1 minute after end of blood sampling were lower in 2ml of 50% (1.0g) sucrose group (0 (0-7) compared to placebo group[(2 (0-7), p = 0.05] |
| Stevens 1999 | 122 neonates, 27 - 31 weeks gestational age, less than 28 days of age | Heel Lance | Prone positioning 30 minutes prior to heel lance
Pacifier dipped in sterile water and placed into the mouth 2 minutes prior to heel lance Pacifier dipped in 24% sucrose and placed into the mouth 2 minutes prior to heel lance Control:Containment in SnuggleUp device (n = 122) NB: All infants were contained in SnuggleUp device |
Premature Infant Pain Profile(PIPP) scores at 30 and 60 seconds | Reported Means, SD | Main effect of treatment for mean PIPP scores, [F (16.20), p < 0.0001]. Post hoc analysis revealed significant reduction in PIPP scores 30 seconds after heel lance in sucrose group (pacifier dipped in 24 % sucrose - estimated at 0.02g), (mean 7.87, SD 3.35), compared to control group [(mean 9.80, SD 3.55), F (24.09), p< 0.0001]. Statistically significant reduction in PIPP scores in pacifier and water group (mean 8.44, SD 3.55) compared to control group [(mean 9.80, SD 3.55), F (9.00), p = 0.003]. Trend towards lower PIPP scores with sucrose and pacifier group compared to water and pacifier group [(F (3.62), p<0.05)] |
Janet Yamada
Nursing Research Program Coordinator
Nursing
The Hospital for Sick Children
555 University Avenue
Toronto
CANADA
M5G 1X8
Telephone 1: 1-416-813-1088
E-mail: janet.yamada@sickkids.ca