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The Use of Oral Sucrose for Procedural Pain Relief in Infants Up to Six Months of Age: A Randomized Controlled Trial
Original Article The Use of Oral Sucrose for Procedural Pain Relief in Infants Up to Six Months of Age: A Randomized Controlled Trial Sally Wilson, MSc(Nsg), BSc(Nsg), RN, RM, Paed Cert, MRCNA,*,† Alexandra P. Bremner, PhD, BSc(Hons), GradDipAppStats, DipEd,‡ Judy Mathews, GradCert(NsgEd), BSc(Nsg), RN, RM, Paed Cert, MRCNA,* and Diane Pearson, GradCert(Paeds), BN, RN, Cert IV (Training and Assessment)* ---
From the *Princess Margaret Hospital for Children, Child and Adolescent Health Service; †School of Nursing and Midwifery, Curtin Health Innovation Research Institute (CHIRI), Curtin University; ‡School of Population Health, The University of Western Australia, Perth, Western Australia. Address correspondence to Sally Wilson, MSc(Nsg), BSc(Nsg), RN, RM, Paed Cert, MRCNA, Department of Nursing Research, Princess Margaret Hospital for Children, GPO Box D184, Perth, Western Australia, 6840. E-mail: [email protected] Received March 22, 2011; Revised August 14, 2011; Accepted August 16, 2011. Supported by a seeding grant from the Princess Margaret Hospital Foundation to S.W. and J.M. 1524-9042/$36.00 Crown Copyright Ó 2013 Published by Elsevier Inc. on behalf of the American Society for Pain Management Nursing doi:10.1016/j.pmn.2011.08.002
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ABSTRACT:
The aim of this study was to evaluate the effectiveness of oral sucrose in decreasing pain during minor procedures in infants of 1-6 months corrected age. A blinded randomized controlled trial with infants aged 4-26 weeks who underwent venipuncture, heel lance or intravenous cannulation were stratified by corrected age into >4-12 weeks and >12-26 weeks. They received 2 mL of either 25% sucrose or sterile water orally 2 minutes before the painful procedure. Nonnutritional sucking and parental comfort, provided in adherence to hospital guidelines, were recorded. Pain behavior was recorded using a validated 10 point scale at baseline, during and following the procedure. Data collectors were blinded to the intervention. A total of 21 and 20 infants received sucrose and water, respectively, in the >4–12-week age group, and 21 and 22, respectively, in the >12–26-week age group. No statistical differences were found in pain scores between treatment and control groups at any data collection points in either age group. Infants aged >4-12 weeks who did nonnutritional sucking showed statistically significantly lower median pain scores at 1, 2, and 3 minutes after the procedure than those who did not suck. Infants aged >426 weeks exhibited pain behavior scores that indicated moderate to large pain during painful procedures; however, there was insufficient Pain Management Nursing, Vol 14, No 4 (December), 2013: pp e95-e105
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evidence to show that 2 mL 25% sucrose had a statistically significant effect in decreasing pain. Infants should be offered nonnutritional sucking in compliance with the Baby Friendly Health Initiative during painful procedures. Crown Copyright Ó 2013 Published by Elsevier Inc. on behalf of the American Society for Pain Management Nursing Reducing pain is recognized as a significant goal in decreasing disruption to infants’ physiologic and behavioral homeostasis while in health care settings. Analgesia is not provided routinely to infants up to 6 months of age who undergo painful procedures such as venipuncture, heel lance, and intravenous cannulations (Harrison, Loughnan, Manias, & Johnston, 2009; Macintyre, Schug, Scott, Visser, & Walker, 2010; Paediatrics & Child Health Division, Royal Australasian College of Physicians, 2005). Although topical anesthetic creams are available and some are suitable for infants in the neonatal period, the cream has to be applied $30 minutes before the procedure (Anaesthetics: amethocaine (skin), 2011), time which is not always available to clinicians. Oral sucrose is an effective analgesic when used for painful procedures in the neonatal population (Stevens, Yamada, & Ohlsson, 2010), but the evidence of its effect in infants older than 28 days is unclear. Oral sucrose alleviates pain by two mechanisms. The primary mechanism is the release of an endogenous opioid, and the effects are mediated by endogenous opioid pathways activated by the sweet taste (Kracke, Uthoff, & Tobias, 2005). This causes an analgesic effect which peaks at 2 minutes following administration and lasts for 5 minutes (Blass & Shah, 1995; Harrison, Johnston, & Loughnan, 2003). Sucrose also has an immediate short-term attention-gaining response due to its strong taste which results in instant calming and cessation of crying (Barr, Young, Wright, Gravel, & Alkawaf, 1999). Studies in which sucrose was administered via nasogastric tube (Ramenghi, Evans, & Levene, 1999) and where less sweet solutions were administered (Barr et al., 1999; Ramenghi, Griffith, Wood, & Levene, 1996) did not show decreases in pain response, therefore supporting the belief that the sweet taste is the effective mediator and not systemic absorption. Taste receptors that detect sweetness are found at the anterior tip of the tongue (Gibbins & Stevens, 2001). The calming effect of sucrose has been shown to diminish by 6 weeks of age (Barr et al., 1999). Also, age and maturation appear to decrease the efficacy of sucrose as an analgesic, although there is a trend toward greater efficacy with higher concentrations of sucrose (Gibbins & Stevens, 2001). Research in rats indicates that sucroseinduced analgesia is age dependent, which may be related to developmental changes in endogenous
analgesic mechanisms and developmental modulation of the interaction between gustatory and painmodulatory pathways (Anseloni, Weng, Terayama, Letizia, Davis, Ren, Dubner, & Ennis, 2002). Whether this translates to humans is unknown, and the upper age limit of effect from sucrose is yet to be established. Harrison et al. (2010) published a systematic review of the efficacy of sweet solutions for analgesia after immunization in infants aged 1-12 months. They reported on 14 randomized controlled trials that used either oral sucrose or glucose solutions ranging from 12% to 75%. The effect on incidence of crying, cry duration, behavioral pain scores, and other physiologic measures, such as heart rate, were discussed. Twelve of the studies compared sucrose or glucose with water, two studies used standard care as the comparator, and several studies also included nonnutritional sucking, parental comfort, or topical anesthetic cream. Following meta-analyses of up to six studies, the authors reported that the oral sweet solutions provided statistically significant reductions in crying incidence and cry duration during or after immunizations compared with water or standard care. Because crying is not a symptom that is exclusive to pain, and discomfort other than pain can contribute to an infant’s crying, composite behavioral pain scales were also used as outcome measures in seven of the studies included in the systematic review (Harrison et al., 2010). In all but one of those seven studies (Lewindon, Harkness, & Lewindon, 1998) the pain scales were valid reliable tools and appropriate for use as measures of pain in infants. Five studies reported reductions in pain scores during or after immunizations when infants received sucrose (12%-75%) compared with water. One study reported a reduction in pain scores when 1 mL 30% glucose was combined with a topical anesthetic compared with water and topical placebo (Lindh, Wiklund, Blomquist, & H akansson, 2003), and a further study showed no difference in pain scores following administration of 12% sucrose compared with water (Poulsen, 2009). Pain scores after immunization were further decreased when nonnutritional sucking and parental comfort were provided (Reis, Roth, Syphan, Tarbell, & Holubkov, 2003). Authors of a later study reported no differences in pain scores or crying time in infants aged 2, 4, or 6 months receiving 2 mL of either water or 50% or 75%
Oral Sucrose for Procedural Pain in Infants
sucrose before immunization. However, they reported a significant difference in pain scores when parental comfort was provided (Curry, Brown, & Wrona, 2012). A limitation of their study was that the pain score was recorded only at 3 minutes after the injection; earlier pain recordings may have provided different information. There are limited studies that look at the effectiveness of oral sweet solutions on painful procedures other than immunizations in infants beyond neonatal age. Rogers, Greenwald, Deguzman, Kelley and Simon (2006) reported no effect on behavioral pain scores, the presence of crying, or the time for the infant to return to the baseline behavioral state in 80 infants aged 0-90 days after urethral catheterization when comparing 2 mL 24% sucrose with water. Curtis, Jou, Ali, Vandermeer and Klassen (2007) studied the effect of 44% sucrose with and without nonnutritional sucking compared with water with and without nonnutritional sucking when 84 infants aged 0-6 months underwent venipuncture. Outcome measures were a composite behavioral pain scale (FLACC), cry duration, and heart rate. Similarly to Rogers, they reported no statistically significant differences in pain scores or heart rate between sucrose and water groups nor between use of nonnutritional sucking and those who did not use a pacifier. However, the difference in crying time was statistically significant between those who used a pacifier and those who did not (143.3 s [SD 101.7] and 229.1 s [SD 90.6], respectively; p ¼ .0001). On subgroup analysis, stratified by age, use of a pacifier reduced crying time by 123.9 seconds (p < .003) in infants aged 1-3 months. Pain scores were not collected during the procedure, only before the venipuncture commenced and between 30 seconds and 1 minute after completion of the procedure, which may have contributed to the lack of significant findings between pain scores. The authors concluded that the benefits of using sucrose alone as an analgesic required further investigation, but when sucrose was used in conjunction with a pacifier it appeared to provide additional benefit in infants aged 1-3 months. The results need to be interpreted with caution, because only crying time was significantly reduced and the number of infants in the 1–3-month group was only 28. Other studies that have reported the effects of sucrose in infants have sample populations that are predominantly neonates, and subgroup analyses have not been provided for infants older than 28 days (Harrison et al., 2003; Harrison, Johnston, Loughnan, & Manias, 2005; Mucignat et al., 2004). Despite the lack of evidence of the effectiveness of oral sweet solutions on pain during procedures other than immunizations in infants older than 28 days, health
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services (Boston Medical Center Pediatrics, 2010) and professional organizations (Paediatrics & Child Health Division, Royal Australasian College of Physicians, 2006; Watson, 2008) recommend its use in infants up to 3 months in age. The aim of the present study was to add to the knowledge of effectiveness of sucrose in infants 1-3 months of age (corrected) and 3-6 months of age (corrected) for use in decreasing pain during minor procedures. The results of this study will assist in guiding practice to relieve pain for this group of infants.
METHODS A blinded randomized controlled trial was conducted. Parents of infants aged from 4 weeks to 26 weeks (corrected age) who were admitted to an infants’ ward in a tertiary pediatric hospital in Western Australia and underwent a painful procedure of venipuncture or heel lance for blood sampling or intravenous cannulation were invited to consent to their infants’ participation in the study. Infants’ corrected ages were used as a criterion for eligibility, because it is thought that sucrose-induced analgesia may be associated with developmental changes related to age (Anseloni et al., 2002). It has been established that sucrose is effective in the neonatal population; therefore, possible confounding was reduced by ensuring that preterm infants older than 28 days were not included in the sample. The infants were stratified by corrected age into 29 days (>4 wk) to 12 weeks of age and those >12 weeks to 26 weeks of age. Every infant’s age was calculated by subtracting the number of weeks born before 40 weeks of gestation from the chronological age (Committee on Fetus and Newborn American Academy of Pediatrics, 2004). Infants were excluded if they were receiving nothing by mouth, receiving intravenous analgesia or sedation, fructose or sucrose intolerant, or had altered gag or swallow reflex, prior exposure to methadone (during the antenatal period), or where response to painful stimuli may be altered by a neuromuscular disease. Interventions Infants received 2 mL of either 25% sucrose or sterile water via syringe onto the anterior portion of the tongue over 30 seconds by the nurse caring for the infant. After administration of the oral solution, 2 minutes elapsed before commencing the procedure. Other than administration of the intervention, standard care was provided. Because the study hospital adhered to the principles of family-centered care and BabyFriendly Health Initiatives (1991), standard care included parents’ ability to be present or leave as they
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wished during the procedure, and the use of pacifiers occurred only with parental permission. They were offered by nurses present to those infants who normally used a pacifier and were crying. Venipunctures and heel lances were carried out by three competent children’s phlebotomists. Intravenous cannulations were done by resident doctors assigned to the ward. Infants were lying supine in their cot, swaddled, with the limb used for the painful procedure exposed, which was held by a phlebotomist not doing the procedure or the primary nurse caring for the infant, as consistent with standard care. Blinding and Randomization Infants were randomly assigned to receive an intervention of either sucrose or sterile water. Permuted block randomization was computer generated by the clinical trials pharmacist to ensure that roughly equal numbers of participants were allocated to each comparison group. The clinical trials pharmacist organized envelopes with the unique trial identification that appeared to be identical except for a sequential number on each. Once ascertained that an infant would have a painful procedure, the nurse opened the next envelope in sequence, which contained a syringe prepared by the pharmacists with either 2 mL of sucrose or 2 mL of sterile water. The codes remained unknown to anyone but the pharmacists until the trial was completed. The nurse who administered the intervention did not collect the data. Both data collectors were blinded to the intervention and were not involved in the care of the infants. Data Collection Pain was recorded using the Children’s and Infant’s Postoperative Pain Scale (CHIPPS) (Buttner & Finke, 2000). The scale ranges from 0 (no pain) to 10 (maximum pain) and measures the following five behavioral parameters of pain: crying, facial expression, posture of the trunk, posture of the legs, and motor restlessness (Table 1). CHIPPS has been reported as a reliable and valid tool for use in infants with internal consistency, interrater reliability, construct validity (Buttner & Finke), specificity, and sensitivity (Suraseranivongse, Kaosaard, Intakong, Pornsiriprasert, Karnchana, Kaopinpruck & Sangjeen, 2006) having been established. CHIPPS has been validated against the Neonatal Infant Pain Scale (Alves et al., 2008) and the Modified Behavioral Pain Scale (Buttner & Finke, 2000). An infant who is assumed to not have pain will score <4 points on CHIPPS, and a score of >3 points may be induced by pain or by other influences on the child’s comfort (Lindh et al., 2003).
TABLE 1. Children’s and Infant’s Postoperative Pain Scale (CHIPPS) Item Crying Facial expression Posture of the trunk Posture of the legs Motor restlessness
Structure
Points
None Moaning Screaming Relaxed/smiling Wry mouth Grimace (mouth and eyes) Neutral Variable Rearing up Neutral/released Kicking about Tightened legs None Moderate Restless
0 1 2 0 1 2 0 1 2 0 1 2 0 1 2
From ‘‘Analysis of behavioural and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young children: A comprehensive report on seven consecutive studies,’’ Buttner W. & Finke W. (2000), Paediatric Anaesthesia, 10(3), 315. Copyright 2000 by John Wiley and Sons. Reprinted with permission.
A baseline pain measurement was collected before the procedure and at the following points during the procedure: when the skin was swabbed, when the needle/lancet punctured the skin, and at blood draw or when the trocar was removed from the cannula. Completion of the procedure was denoted by cessation of handling by the phlebotomist or the doctor, at which point timing for postprocedure observations began. Postprocedure assessments occurred at 1, 2, and 3 minutes. If a second attempt of the procedure was required or if the procedure lasted for >5 minutes (7 minutes after administration of the intervention), the infant was excluded from the trial. Further observational data were collected at the same procedural and time points as pain scores and included the child’s disposition, occurrence of sucking, and whether comfort was being offered. Sucking included breastfeeding and nonnutritive sucking, such as use of a pacifier or sucking on a thumb or fist. Comfort was defined as any cuddling, patting, or verbal interaction between the infant and a parent, nurse, or other person. All infants admitted to the study ward who were likely to have a painful procedure were identified by the ward staff, and one of three registered nurses who were members of the research team was notified during study hours (weekdays, 07:00-18:00). The researcher screened the infant for eligibility and recruited infants. The study was explained to the family by the researcher, a parent information sheet was
Oral Sucrose for Procedural Pain in Infants
provided, and written consent was obtained. Information relating to medical history and infant’s age (actual and corrected) was recorded. Over the study period, data were collected by two nurses. Before commencement of the study, the nurses spent time in the clinical area to ensure that use of the tool was congruent with current practice. The interrater agreement for the nurses collecting data was found to have an intraclass correlation of 0.926 (p < .001; 95% confidence interval 0.8740.957). Data were recorded on a data collection sheet and entered into SPSS for Windows version 17.0.1 (Chicago, IL) by the principal researcher. Ethical Considerations Human Research Ethics Committee approval was granted by the study hospital. Participants’ parents were informed that they could choose not to have their infant participate in the study and it would not compromise the care of their child or their family and confidentiality was assured. Data Analysis Statistical Methods. Summary data were obtained for each treatment group by calculating means and SDs for continuous data and frequencies for categoric data. Demographic and other baseline variables were compared between treatment and placebo groups in each age group with the use of t tests or c2 tests as appropriate. Independent t tests were used to check for differences between time at each data collection point for each group. Because the distributions of pain scores were not normally distributed, Mann-Whitney tests were performed to compare the pain scores between groups at each data collection point for each group. Similarly, Mann-Whitney tests were performed to ascertain whether provision of nonnutritional sucking had an effect on pain scores. Independent t tests were used to ascertain differences between mean pain scores in infants who received sucrose and those who received water when ages were grouped (>4 weeks to 26 weeks of age, corrected) and to assess whether there was a difference in pain scores when nonnutritional sucking was provided compared with no sucking. A significance level of p ¼ .05 was used for all statistical tests. Sample Size. Sample size was based on the primary outcome of interest, the effect of sucrose on pain reduction. A reduction of 2 points was deemed to be clinically relevant. Based on earlier measurements of pain using a 10-point scale it was estimated that the SD of pain scores using CHIPPS was 2.2 (Bauer, Ketteler, Hellwig, Laurenz, & Versmold, 2004; Liu, Lin, Chou, & Lee, 2010). Assuming an alpha level of 0.05 and
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a power of 80%, a total sample of 20 infants was required to be able to detect a 2-point average difference on CHIPPS between two groups with the use of an independent t test (Power and Sample Size Program PS version 3.0.5).
RESULTS From August 2007 to January 2009, 111 infants were assessed for eligibility into the study, and 21 were excluded from this initial group (Fig. 1). Ninety infants were randomized to either the intervention or the control group. In age group 1 (>4-12 weeks), 22 infants were allocated and received sucrose, and 23 infants were allocated and 21 received water; in age group 2 (>12-26 weeks), 22 infants were allocated and 21 infants received sucrose, and 23 were allocated and received water. Three infants were unable to be included once recruited, because the researchers were unavailable when the procedures were being done. There were two adverse events that resulted in two infants being removed from the study. One, in age group 1, vomited after administration of the 2 mL sucrose, and the other, in group 2, coughed and gagged during administration of water, so administration was stopped. Both infants recovered spontaneously and the events were not deemed to be clinically significant. Data from another infant were removed from the analysis because the procedure lasted >7 minutes from the time intervention was administered. All remaining infants completed the study. Twenty-one received sucrose and 20 received water in the >4–12 weeks age range, and 21 and 22 received sucrose and water, respectively, in the >12–26-week age group. Figure 1 provides the study flow diagram. Comparison of demographic characteristics showed no significant differences between the two treatment groups. Provision of comfort by parent in group 2 at baseline, one and three minutes post procedure were significantly different (c2 ¼ 4.53; p ¼ .033; c2 ¼ 5.53; p ¼ 0.019; and c2 ¼ 4.56; p ¼ 0.033; respectively; Table 2). Time (in minutes and seconds) was calculated for each subsequent data collection point after intervention administration. No statistically significant differences were found in the times between sucrose and water groups in either age group nor between those who received nonnutritional sucking and those who did not. No statistical differences were found in pain scores between the intervention and control groups at any data collection point for either age group (Table 3). The infants aged >4-12 weeks that received sucrose had a lower median pain score at time of blood draw than those who had water (5, interquartile range
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Infants assessed for eligibility n = 111 Excluded (n=21) • Not meeting inclusion criteria (n=5) • Declined to participate (n=5) • Parents/researcher not available to seek consent (n=11) • Other reasons (n=0)
Eligible, consented, randomly assigned n = 90
Strata 1: >4 weeks-12 weeks n = 45
Allocated to sucrose n=22 • Received allocated intervention n=22 • Did not receive allocated n=0
Discontinued intervention (vomited) n=1
Analyzed n=21 • Excluded from analysis n=0
Strata 2: >12 weeks-26 weeks n = 45
Allocated to water n=23 • Received allocated intervention n=21 • Did not receive allocated intervention (researcher not available) n=2
Allocated to sucrose n=22 • Received allocated intervention n=21 • Did not receive allocated intervention (researcher not available) n=1
Discontinued intervention
Discontinued intervention
n=0
n=0
Analyzed n=20 • Excluded from analysis (procedure lasted > 7 min) n=1
FIGURE 1.
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[IQR] 6; and 7, IQR 7; respectively); similarly, the older group had a difference in median pain scores of 2 at time of needle insertion (5, IQR 6; and 7, IQR 5; respectively). Statistical differences in median pain scores were found between infants who did nonnutritional sucking and those who did not in age group 1 at 1 (z ¼ 2.83; p ¼ .005), 2 (z ¼ 2.00; p ¼ .045), and 3 minutes (z ¼ 2.10; p ¼ .036) after the procedure, with infants who did nonnutritional sucking having lower pain scores at each data collection point (Fig. 2). There were no statistical differences in times from intervention between all infants who had sucrose (n ¼ 42) compared with all infants who received water (n ¼ 42). There was a difference in pain scores at time of skin swab, with those who had water scoring higher than those who had sucrose (t ¼ 2.3; p ¼ .024). No other statistically significant differences were found (Fig. 3). The number of infants who used nonnutritional sucking at the various data collection points ranged from 36 to 50, with those who did not suck ranging from 33-48. Statistically significant differences in pain scores between infants who undertook
Allocated to water n=23 • Received allocated intervention n=23 • Did not receive allocated intervention n=0
Discontinued intervention (coughed & gagged) n=1
Analyzed n=21
Analyzed n=22
• Excluded from analysis n=0
• Excluded from analysis n=0
Flow diagram.
nonnutritional sucking and those who did not were found at 1 and 2 minutes after procedure (p values .043 and .027, respectively). Those provided with nonnutritional sucking recorded lower pain scores (Fig. 4).
DISCUSSION Results of this study show that infants undergoing venipuncture, intravenous cannulation, or heel lance procedures experience moderate to large pain (Blass & Shah, 1995; Boston Medical Center Pediatrics, 2010) with median pain scores as high as 7.5 (IQR 5) during skin penetration in infants >4-12 weeks old. Pain scores of 10 were recorded for ten infants during skin penetration by a needle, a further ten infants had pain scores of 9, and nine infants had pain scores of 10 during blood draw. The high pain scores recorded for this number of infants indicates that some type of analgesia needs to be used, particularly for infants who undergo painful procedures frequently. A strength of this study was the collection of pain scores during the minor procedures along with the actual time from administration of the intervention. The
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TABLE 2. Infants’ Characteristics Age Group 1, >4-12 wk Sucrose (n ¼ 21)
Age Group 2, >12-26 wk
Water (n ¼ 20)
Sucrose (n ¼ 21)
Water (n ¼ 22)
Mean (SD) Corrected age (wk) Actual age (wk) Weight (g)
7.7 (2.58) 9.4 (4.75) 4,569 (970)
7.2 (2.84) 8.1 (2.63) 4,384 (807)
17.1 (3.69) 18.4 (3.81) 5,917 (1519)
18.5 (4.40) 20.1 (4.38) 6,209 (1102)
n (%) Male gender Nonnutritional sucking* Comfort by parent* Minor painful procedure Venipuncture Heelprick IV cannulation Other Reason for admission Gastrointestinal Respiratory Neurological Infection/sepsis Cardiac Other
12 (57.1) 8-12 (38-57) 7-13 (33-62)
8 (40) 8-12 (40-60) 8-17 (40-85)
10 (47.6) 11-15 (52-74) 4-12 (19-57)†
16 (72.7) 9-14 (41-64) 11-19 (50-86)†
10 (47.6) 9 (42.9) 1 (4.8) 1 (4.8)
7 (35.0) 12 (60.0) 1 (5.0) 0
11 (52.4) 8 (38.1) 0 2 (9.5)
13 (59.1) 3 (13.6) 1 (4.5) 5 (22.7)
9 (42.9) 5 (23.8) 1 (4.8) 2 (9.5) 3 (14.3) 1 (4.8)
1 (5.0) 6 (30.0) 4 (20.0) 4 (20.0) 2 (10.0) 3 (15.0)
6 (28.6) 5 (23.8) 6 (28.6) 3 (14.3) 1 (4.8) 0
9 (40.9) 4 (18.2) 5 (22.7) 3 (13.6) 1 (4.5) 0
*Range of numbers provided, because the number of infants using a pacifier and receiving comfort from a parent varied at each data collection point. † p < .05 for comfort by parent for infants in stratum 2 between water and sucrose at baseline, 1 and 3 minutes post procedure
TABLE 3. Time from Intervention and Pain Scores for Interventions for Each Age Group Pain Score, Median (IQR) Time from Intervention (min:s), Mean (SD) Age Group 1: >4-12 wk corrected Baseline Skin swab Needle insertion Blood draw Completion of procedure 1 min after procedure 2 min after procedure 3 min after procedure Age Group 2: >12-26 wk corrected Baseline Skin swab Needle insertion Blood draw At completion of procedure 1 min after procedure 2 min after procedure 3 min after procedure
Sucrose
Water
p Value
2:04 (0:47) 2:45 (1:09) 4:18 (1:54) 5:54 (2:08) 6:54 (2:07) 7:54 (2:07) 8:54 (2:07)
0.0 (2) 1.0 (5) 7.0 (5) 5.0 (6) 5.0 (5) 1.5 (3) 1.0 (2) 0.0 (1)
0.0 (3) 3.0 (6) 7.5 (5) 7.0 (7) 5.0 (5) 3.0 (5) 0.0 (4) 0.0 (1)
.62 .25 .22 .31 .69 .36 .92 .95
2:36 (1:02) 3:14 (1:14) 4:33 (1:25) 5:53 (1:54) 6:56 (2:00) 7:53 (1:54) 8:57 (1:58)
0.0 (2) 1.0 (3) 5.0 (6) 5.0 (6) 4.0 (5) 1.0 (3) 1.0 (2) 1.0 (2)
1.0 (1) 2.5 (6) 7.0 (5) 6.0 (3) 3.5 (5) 2.0 (5) 1.0 (1) 0.0 (2)
.60 .13 .80 .69 .67 .33 .29 .83
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FIGURE 2. no pain.
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Pain scores for infants by nonnutritional sucking and age. *p < .05. Pain score #3 (below dashed line) signifies
FIGURE 3. - Pain scores for all infants by intervention. *p < .05. Pain score #3 (below dashed line) signifies no pain.
length of time from administration of intervention to needle penetration of the skin was an average 3 minutes 12 seconds, 4 minutes 41 seconds to blood draw, and 6 minutes 8 seconds to completion of the procedure. If it is accepted that the sucrose effect peaks at 2 minutes and lasts only 5-8 minutes (Buttner & Finke, 2000), the effects of sucrose would have been diminished when the blood was drawn. Nevertheless, the pain scores of infants who received sucrose were lower than those who received water in both groups at needle insertion and blood draw, although the differences were not statistically significant. Because the average time for the procedures was 3 minutes from needle insertion or 6 minutes from administration of the intervention, the effects of sucrose would have been minimal by the time the procedures were completed. This may explain why the pain scores were the same on completion of the procedure for infants that received water and sucrose in both age groups. A difference in pain scores was shown when data on all infants were analyzed together at the time the infants’ skin was swabbed. The mean pain score was 3.2
Oral Sucrose for Procedural Pain in Infants
FIGURE 4. - Pain scores for all infants by nonnutritional sucking. *p < .05. Pain score #3 (below dashed line) signifies no pain.
for those who received water. Although this score reflects an influence on the child’s comfort, an infant who does not have pain would score <4 (Dilli, Kucuk, & Dallar, 2009; Poulsen, 2009). The lower mean score (1.9) of those who had sucrose may represent the calming effect of sucrose to the cold stimulus of the alcohol skin swab at the 2-minute mark. The strength of sucrose used in this study was 25%, because this was the readily available stock strength provided by the pharmacy in the study hospital. Strengths of 24%-75% have been shown to be effective in reducing pain scores in infants during immunization, with mixed results when the lower strength of 12% was administered (Curtis et al., 2007). Increasing the strength of sucrose may not make any difference to behavioral pain scores in infants during painful procedures other than immunization, because 44% sucrose was not shown to reduce the pain score in a randomized controlled trial in infants aged 1-6 months during venipuncture; however, crying time was reduced (Buttner & Finke, 2000). Significant differences in pain scores were shown in group 1 between infants that received nonnutritional sucking and those who did not at 1, 2, and 3 minutes after the procedure. However, the median pain score was 3 at 1 minute after the procedure, which may indicate an alteration in comfort but does not signify pain (Curtis et al., 2007; Harrison et al., 2010). Similarly, a significant difference was found in mean pain scores
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when results for all infants were analyzed together, with those who did not suck having a higher pain score at 1 and 2 minutes after the procedure. Again, the highest mean pain score was 3.03 at 1 minute, which may indicate that infants who do not use a pacifier take longer to settle. Although not significant, nonnutritional sucking showed a difference of 2 points on the pain scale on completion of procedure in the younger infants and at blood draw in the older infants. As provision of a pacifier is a inexpensive intervention and has been shown to reduce crying time during venipuncture and immunizations (Reis et al., 2003); ensuring adherence to the BabyFriendly Health Initiative (1991) and parental wishes, this option should be considered when any painful procedure is being performed. Whether comfort was provided to the infants during the painful procedure was recorded. However, there were insufficient incidents of comfort by a parent to undertake meaningful analysis. Although the nurses and phlebotomists provided some comfort, actually cuddling the infant during the procedure was never done by staff or parents. Reis et al. (2003) found a combination of parental holding, oral tactile stimulation, and sucrose reduced crying time in infants during immunization. Although not recorded as part of the study, it was noted that parents often were not present when their infant was undergoing the procedure, which is consistent with the practice of family-centered care, where parents can stay or leave as they wish during procedures. Because age appeared to make no difference, the groups were combined and the larger sample of 84 infants was analyzed. Because the only statistically significant differences in pain scores were at data collection points when infants pain scores were <4, a reduction in infants’ settling is reflected rather than a reduction in pain. The nonsignificant differences in pain scores during the procedure add to the body of knowledge of the effectiveness of sucrose in reducing pain during minor procedures in infants 1-6 months old. Study Limitations The numbers in each group are similar to other studies that have shown an effect on behavioral pain scores between sucrose and water during venipuncture and heel lance in the neonatal population (Hatfield, 2008; Hatfield, Gusic, Dyer, & Polomano, 2008). Although the sample was sufficiently powered for the primary outcome, there were insufficient numbers for subgroup analyses to ascertain whether sucking or comfort had an effect on pain scores. The sample was a convenience sample with several potentially available infants being missed. The
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researchers were not available during the night nor over the weekends. As much demographic information was collected as possible on those infants that were missed, and there is nothing to suggest that they were different from the infants enrolled in the study. Randomization of intervention to those enrolled should have reduced any recruiting bias. The dose of sucrose was standardized for all infants and not based on the infant’s weight despite the infants’ weights ranging from 2,920 to 6,800 grams (group 1) and 3,315 to 9,700 grams (group 2). Studies that have based the dose of sucrose on infants’ weight have shown reductions in behavioral pain scores during immunizations (Blass & Shah, 1995). If the release of endogenous opioids is activated by the sweet taste (Duff, Louw, Loftus-Hills, & Morrell, 2001), then calculating the volume of sucrose based on an infant’s weight is unlikely to affect this mechanism. Clinical Implications While evidence is still unavailable of the effectiveness of oral sucrose during painful procedures other than immunizations, nurses should consider applying a topical anesthetic cream when there is time, because there is sufficient evidence to support its effectiveness in reducing pain in infants aged 1-6 months. When there is not time for the application of a topical anesthetic, because sucrose is inexpensive, readily available, and easy to use, and it lacks documented side effects, nurses may offer the hospital’s stock strength of oral sucrose for all painful procedures despite no clear evidence as to its effectiveness. However, three things should be considered: First, use oral sucrose in combination with a pacifier only with parental permission; second, consider beginning the procedure 1 minute after administration of sucrose so that the effect of sucrose, which peaks at 2 minutes, occurs when the
needle penetrates the infant’s skin; and third, consider administering 2 mL sucrose every 2 minutes until the procedure is completed to maintain the possible release of endogenous opioids. Further studies should try to ensure that the most painful part of the procedure occurs 2 minutes after administration of the sucrose or continue to provide sucrose every 2 minutes during the procedure to maximize the potential effects of sucrose. A composite pain tool that has been validated for use in the infant age group should be an outcome measure for all future research in this area.
CONCLUSION Infants do suffer pain when undergoing minor procedures. In this study there was insufficient evidence to show that 2 mL 25% oral sucrose administered 2 minutes before the onset of venipuncture, intravenous cannulation, or heel lance made a statistically significant difference to pain scores when measured with a validated behavioral pain scale in infants aged >412 weeks or >12-26 weeks corrected age. There were statistically significant differences in pain scores at 1, 2, and 3 minutes after the procedure for infants aged >4-12 weeks and at 1 and 2 minutes for all infants, with those undertaking nonnutritional sucking having lower pain scores at the 5% significance level. However, this probably reflects comfort and earlier settling, because the pain scores were <4 at each data collection point. Acknowledgments The researchers thank the families who agreed to participate, Margaret Shave and the clinical trials pharmacists, Jenni Corrigan and the phlebotomists and Tracey Maron and staff of the study ward.
REFERENCES Alves, M. M. O., Carvalho, P. R. A., Wagner, M. B., Castoldi, A., Becker, M. M., & Silva, C. C. (2008). Cross-validation of the children’s and infants’ postoperative pain scale in Brazilian children. Pain Practice, 8(3), 171–176. Anaesthetics: Amethocaine (skin) (2011). Retrieved August 11, 2011, from Australian Medicines Handbook, http:// www.amh.net.au.pklibresources.health.wa.gov.au Anseloni, V. C. Z., Weng, H.-R., Terayama, R., Letizia, D., Davis, B. J., Ren, K., Dubner, R., & Ennis, M. (2002). Agedependency of analgesia elicited by intraoral sucrose in acute and persistent pain models. Pain, 97, 93–103. Baby-Friendly Health Initiative (1991). The ten steps to succesful breastfeeding. Retrieved October 15, 2010, from http://www.bfhi.org.au/text/bfhi_ten_steps.html Barr, R. G., Young, S. N., Wright, J. H., Gravel, R., & Alkawaf, R. (1999). Differential calming responses to sucrose
taste in crying infants with and without colic. Pediatrics, 103(5 e68), 1–9. Bauer, K., Ketteler, J., Hellwig, M., Laurenz, M., & Versmold, H. (2004). Oral glucose before venipuncture relieves neonates of pain, but stress is still evidenced by increase in oxygen consumption, energy expenditure, and heart rate. Pediatric Research, 55(4), 695–700. Blass, E. M., & Shah, A. (1995). Pain-reducing properties of sucrose in human newborns. Chemical Senses, 20, 29–35. Boston Medical Center Pediatrics (2010). Pediatricspainfree program Retrieved October 8, 2010, from http:// www.bmc.org/pediatrics-painfree/medicalprofessionals/ pharmacologicalpainrelief.htm#1suc Buttner, W., & Finke, W. (2000). Analysis of behavioural and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young
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children: A comprehensive report on seven consecutive studies. Paediatric Anaesthesia, 10(3), 303–318. Committee on Fetus and Newborn American Academy of Pediatrics (2004). Age terminology during the perinatal period. Pediatrics, 114(5), 1362–1364. Curry, D. M., Brown, C., & Wrona, S. (2012). Effectiveness of oral sucrose for pain management in infants during immunizations. Pain Management Nursing, 13(3), 139–149. Curtis, S., Jou, H., Ali, S., Vandermeer, B., & Klassen, T. (2007). A randomized controlled trial of sucrose and/or pacifier as analgesia for infants receiving venipuncture in a pediatric emergency department. BMC Pediatrics, 7(1), 27, Retrieved from http://www.biomedcentral.com/ 1471-2431/7/27. Dilli, D., Kucuk, Z. G., & Dallar, Y. (2009). Interventions to reduce pain during vaccination in infancy. Journal of Pediatrics, 154, 385–390. Duff, L., Louw, G., Loftus-Hills, A., & Morrell, C. (2001). Clinical practice guidelines: The recognition and assessment of acute pain in children. Retrieved October 15, 2010, from http://www.rcn.org.uk/__data/assets/pdf_file/0007/109825/ 001309.pdf Gibbins, S., & Stevens, B. (2001). Mechanisms of sucrose and nonnutritive sucking in procedural pain management in infants. Pain Research Management, 6(1), 21–28. Harrison, D., Johnston, L., & Loughnan, P. (2003). Oral sucrose for procedural pain in sick hospitalized infants: A randomized-controlled trial. Journal of Paediatrics & Child Health, 39(8), 591–597. Harrison, D., Johnston, L., Loughnan, P., & Manias, E. (2005). Erratum: Re: Oral sucrose for procedural pain in sick hospitalized infants: A randomized-controlled trial[Journal of Paediatrics & Child Health 2003, 39, 591–7]. Journal of Paediatrics & Child Health, 41, 535. Harrison, D., Loughnan, P., Manias, E., & Johnston, L. (2009). Analgesics administered during minor painful procedures in a cohort of hospitalized infants: A prospective clinical audit. Journal of Pain, 10(7), 715–722. Harrison, D., Stevens, B., Bueno, M., Yamada, J., AdamsWebber, T., Beyene, J., & Ohlsson, A. (2010). Efficacy of sweet solutions for analgesia in infants between 1 and 12 months of age: A systematic review. Archives of Disease in Childhood, 95(6), 406–413. Hatfield, L. A. (2008). Sucrose decreases infant biobehavioral pain response to immunizations: A randomized controlled trial. Journal of Nursing Scholarship, 40(3), 219–225. Hatfield, L. A., Gusic, M. E., Dyer, A. M., & Polomano, R. C. (2008). Analgesic properties of oral sucrose during routine immunizations at 2 and 4 months of age. Pediatrics, 121(2), e327–334. Kracke, G. R., Uthoff, K. A., & Tobias, J. D. (2005). Sugar solution analgesia: The effects of glucose on expressed mu opioid receptors. Anesthesia & Analgesia, 101(1), 64–68. Lewindon, P., Harkness, L., & Lewindon, N. (1998). Randomized controlled trial of sucrose by mouth for the relief of infant crying after immunization. Archives of Disease in Childhood, 78, 453–456. Lindh, V., Wiklund, U., Blomquist, H. K., & H akansson, S. (2003). Emla cream and oral glucose for immunization pain in 3-month-old infants. Pain, 104(1-2), 381–388.
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Liu, M.-F., Lin, K.-C., Chou, Y.-H., & Lee, T.-Y. (2010). Using nonnutritive sucking and oral glucose solution with neonates to relieve pain: A randomised controlled trial. Journal of Clinical Nursing, 19, 1604–1611. Macintyre, P., Schug, S. A., Scott, D. A., Visser, E. J., Walker, S. M., & : APM SE Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (2010). Acute pain management: Scientific evidence, (3rd ed.) Melbourne: ANZCA & FPM. Retrieved from. http://www.anzca.edu.au/resources/books-and-publications/ acutepain.pdf. Mucignat, V., Ducrocq, S., Lebas, F., Mochel, F., Baudon, J. J., & Gold, F. (2004). Effet analgesique de la creme Emla, du saccharose et de leur association pour les injections tude prosous-cutanees chez le nouveau-ne prematur e: E spective de 265 injections [Analgesic effects of oral administration of saccharose solution, local application of Emla and their association for subcutaneous injections of erythropoietin (EPO) in preterm infants: A prospective study]. Archives de Pediatrie, 11(8), 921–925. Paediatrics & Child Health Division Royal Australasian College of Physicians (2005). Guideline statement: Management of procedure-related pain in children and adolescents Retrieved October 12, 2010, from http://www.racp.edu.au/ page/policy-and-advocacy/paediatrics-and-child-health Paediatrics & Child Health Division, Royal Australasian College of Physicians (2006). Guideline statement: Management of procedure related pain in children and adolescents. Journal of Paediatrics & Child Health, 42, S1–S29. Poulsen, M. (2009). Cane sugar unsuitable for use as analgesic in paediatric vaccination. Danish Journal of Nursing, 109(6), 54–57. Ramenghi, L. A., Evans, D. J., & Levene, M. I. (1999). Sucrose analgesia: Absorptive mechanism or taste perception? Archives of Disease in Childhood. Fetal & Neonatal Edition, 80, 146–147. Ramenghi, L. A., Griffith, G. C., Wood, C. M., & Levene, M. I. (1996). Effect of nonsucrose sweet tasting solution on neonatal heel prick responses. Archives of Disease in Childhood. Fetal and Neonatal Edition, 74(2), 129F–131F. Reis, E. C., Roth, E. K., Syphan, J. L., Tarbell, S. E., & Holubkov, R. (2003). Effective pain reduction for multiple immunization injections in young infants. Archives of Pediatrics & Adolescent Medicine, 157(11), 1115–1120. Rogers, A. J., Greenwald, M. H., Deguzman, M. A., Kelley, M. E., & Simon, H. K. (2006). A randomized, controlled trial of sucrose analgesia in infants younger than 90 days of age who require bladder catheterization in the pediatric emergency department. Academic Emergency Medicine, 13(6), 617–622. Stevens, B., Yamada, J., & Ohlsson, A. (2010). Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database of Systematic Reviews, 1, 1–112. Suraseranivongse, S., Kaosaard, R., Intakong, P., Pornsiriprasert, S., Karnchana, Y., Kaopinpruck, J., & Sangjeen, K. (2006). A comparison of postoperative pain scales in neonates. British Journal of Anaesthesia, 97(4), 540–544. Watson, W. (2008). Sucrose analgesia: How sweet it is. Sucrose for procedural pain in infants age 0-6 months. Nurs Aust, 9(2), 16–17, Retrieved from http://www.nursing.edu. au/portal/nursing.aust/nursing.aust/Autumn_2011.html.
From the *Princess Margaret Hospital for Children, Child and Adolescent Health Service; †School of Nursing and Midwifery, Curtin Health Innovation Research Institute (CHIRI), Curtin University; ‡School of Population Health, The University of Western Australia, Perth, Western Australia. Address correspondence to Sally Wilson, MSc(Nsg), BSc(Nsg), RN, RM, Paed Cert, MRCNA, Department of Nursing Research, Princess Margaret Hospital for Children, GPO Box D184, Perth, Western Australia, 6840. E-mail: [email protected] Received March 22, 2011; Revised August 14, 2011; Accepted August 16, 2011. Supported by a seeding grant from the Princess Margaret Hospital Foundation to S.W. and J.M. 1524-9042/$36.00 Crown Copyright Ó 2013 Published by Elsevier Inc. on behalf of the American Society for Pain Management Nursing doi:10.1016/j.pmn.2011.08.002
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ABSTRACT:
The aim of this study was to evaluate the effectiveness of oral sucrose in decreasing pain during minor procedures in infants of 1-6 months corrected age. A blinded randomized controlled trial with infants aged 4-26 weeks who underwent venipuncture, heel lance or intravenous cannulation were stratified by corrected age into >4-12 weeks and >12-26 weeks. They received 2 mL of either 25% sucrose or sterile water orally 2 minutes before the painful procedure. Nonnutritional sucking and parental comfort, provided in adherence to hospital guidelines, were recorded. Pain behavior was recorded using a validated 10 point scale at baseline, during and following the procedure. Data collectors were blinded to the intervention. A total of 21 and 20 infants received sucrose and water, respectively, in the >4–12-week age group, and 21 and 22, respectively, in the >12–26-week age group. No statistical differences were found in pain scores between treatment and control groups at any data collection points in either age group. Infants aged >4-12 weeks who did nonnutritional sucking showed statistically significantly lower median pain scores at 1, 2, and 3 minutes after the procedure than those who did not suck. Infants aged >426 weeks exhibited pain behavior scores that indicated moderate to large pain during painful procedures; however, there was insufficient Pain Management Nursing, Vol 14, No 4 (December), 2013: pp e95-e105
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evidence to show that 2 mL 25% sucrose had a statistically significant effect in decreasing pain. Infants should be offered nonnutritional sucking in compliance with the Baby Friendly Health Initiative during painful procedures. Crown Copyright Ó 2013 Published by Elsevier Inc. on behalf of the American Society for Pain Management Nursing Reducing pain is recognized as a significant goal in decreasing disruption to infants’ physiologic and behavioral homeostasis while in health care settings. Analgesia is not provided routinely to infants up to 6 months of age who undergo painful procedures such as venipuncture, heel lance, and intravenous cannulations (Harrison, Loughnan, Manias, & Johnston, 2009; Macintyre, Schug, Scott, Visser, & Walker, 2010; Paediatrics & Child Health Division, Royal Australasian College of Physicians, 2005). Although topical anesthetic creams are available and some are suitable for infants in the neonatal period, the cream has to be applied $30 minutes before the procedure (Anaesthetics: amethocaine (skin), 2011), time which is not always available to clinicians. Oral sucrose is an effective analgesic when used for painful procedures in the neonatal population (Stevens, Yamada, & Ohlsson, 2010), but the evidence of its effect in infants older than 28 days is unclear. Oral sucrose alleviates pain by two mechanisms. The primary mechanism is the release of an endogenous opioid, and the effects are mediated by endogenous opioid pathways activated by the sweet taste (Kracke, Uthoff, & Tobias, 2005). This causes an analgesic effect which peaks at 2 minutes following administration and lasts for 5 minutes (Blass & Shah, 1995; Harrison, Johnston, & Loughnan, 2003). Sucrose also has an immediate short-term attention-gaining response due to its strong taste which results in instant calming and cessation of crying (Barr, Young, Wright, Gravel, & Alkawaf, 1999). Studies in which sucrose was administered via nasogastric tube (Ramenghi, Evans, & Levene, 1999) and where less sweet solutions were administered (Barr et al., 1999; Ramenghi, Griffith, Wood, & Levene, 1996) did not show decreases in pain response, therefore supporting the belief that the sweet taste is the effective mediator and not systemic absorption. Taste receptors that detect sweetness are found at the anterior tip of the tongue (Gibbins & Stevens, 2001). The calming effect of sucrose has been shown to diminish by 6 weeks of age (Barr et al., 1999). Also, age and maturation appear to decrease the efficacy of sucrose as an analgesic, although there is a trend toward greater efficacy with higher concentrations of sucrose (Gibbins & Stevens, 2001). Research in rats indicates that sucroseinduced analgesia is age dependent, which may be related to developmental changes in endogenous
analgesic mechanisms and developmental modulation of the interaction between gustatory and painmodulatory pathways (Anseloni, Weng, Terayama, Letizia, Davis, Ren, Dubner, & Ennis, 2002). Whether this translates to humans is unknown, and the upper age limit of effect from sucrose is yet to be established. Harrison et al. (2010) published a systematic review of the efficacy of sweet solutions for analgesia after immunization in infants aged 1-12 months. They reported on 14 randomized controlled trials that used either oral sucrose or glucose solutions ranging from 12% to 75%. The effect on incidence of crying, cry duration, behavioral pain scores, and other physiologic measures, such as heart rate, were discussed. Twelve of the studies compared sucrose or glucose with water, two studies used standard care as the comparator, and several studies also included nonnutritional sucking, parental comfort, or topical anesthetic cream. Following meta-analyses of up to six studies, the authors reported that the oral sweet solutions provided statistically significant reductions in crying incidence and cry duration during or after immunizations compared with water or standard care. Because crying is not a symptom that is exclusive to pain, and discomfort other than pain can contribute to an infant’s crying, composite behavioral pain scales were also used as outcome measures in seven of the studies included in the systematic review (Harrison et al., 2010). In all but one of those seven studies (Lewindon, Harkness, & Lewindon, 1998) the pain scales were valid reliable tools and appropriate for use as measures of pain in infants. Five studies reported reductions in pain scores during or after immunizations when infants received sucrose (12%-75%) compared with water. One study reported a reduction in pain scores when 1 mL 30% glucose was combined with a topical anesthetic compared with water and topical placebo (Lindh, Wiklund, Blomquist, & H akansson, 2003), and a further study showed no difference in pain scores following administration of 12% sucrose compared with water (Poulsen, 2009). Pain scores after immunization were further decreased when nonnutritional sucking and parental comfort were provided (Reis, Roth, Syphan, Tarbell, & Holubkov, 2003). Authors of a later study reported no differences in pain scores or crying time in infants aged 2, 4, or 6 months receiving 2 mL of either water or 50% or 75%
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sucrose before immunization. However, they reported a significant difference in pain scores when parental comfort was provided (Curry, Brown, & Wrona, 2012). A limitation of their study was that the pain score was recorded only at 3 minutes after the injection; earlier pain recordings may have provided different information. There are limited studies that look at the effectiveness of oral sweet solutions on painful procedures other than immunizations in infants beyond neonatal age. Rogers, Greenwald, Deguzman, Kelley and Simon (2006) reported no effect on behavioral pain scores, the presence of crying, or the time for the infant to return to the baseline behavioral state in 80 infants aged 0-90 days after urethral catheterization when comparing 2 mL 24% sucrose with water. Curtis, Jou, Ali, Vandermeer and Klassen (2007) studied the effect of 44% sucrose with and without nonnutritional sucking compared with water with and without nonnutritional sucking when 84 infants aged 0-6 months underwent venipuncture. Outcome measures were a composite behavioral pain scale (FLACC), cry duration, and heart rate. Similarly to Rogers, they reported no statistically significant differences in pain scores or heart rate between sucrose and water groups nor between use of nonnutritional sucking and those who did not use a pacifier. However, the difference in crying time was statistically significant between those who used a pacifier and those who did not (143.3 s [SD 101.7] and 229.1 s [SD 90.6], respectively; p ¼ .0001). On subgroup analysis, stratified by age, use of a pacifier reduced crying time by 123.9 seconds (p < .003) in infants aged 1-3 months. Pain scores were not collected during the procedure, only before the venipuncture commenced and between 30 seconds and 1 minute after completion of the procedure, which may have contributed to the lack of significant findings between pain scores. The authors concluded that the benefits of using sucrose alone as an analgesic required further investigation, but when sucrose was used in conjunction with a pacifier it appeared to provide additional benefit in infants aged 1-3 months. The results need to be interpreted with caution, because only crying time was significantly reduced and the number of infants in the 1–3-month group was only 28. Other studies that have reported the effects of sucrose in infants have sample populations that are predominantly neonates, and subgroup analyses have not been provided for infants older than 28 days (Harrison et al., 2003; Harrison, Johnston, Loughnan, & Manias, 2005; Mucignat et al., 2004). Despite the lack of evidence of the effectiveness of oral sweet solutions on pain during procedures other than immunizations in infants older than 28 days, health
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services (Boston Medical Center Pediatrics, 2010) and professional organizations (Paediatrics & Child Health Division, Royal Australasian College of Physicians, 2006; Watson, 2008) recommend its use in infants up to 3 months in age. The aim of the present study was to add to the knowledge of effectiveness of sucrose in infants 1-3 months of age (corrected) and 3-6 months of age (corrected) for use in decreasing pain during minor procedures. The results of this study will assist in guiding practice to relieve pain for this group of infants.
METHODS A blinded randomized controlled trial was conducted. Parents of infants aged from 4 weeks to 26 weeks (corrected age) who were admitted to an infants’ ward in a tertiary pediatric hospital in Western Australia and underwent a painful procedure of venipuncture or heel lance for blood sampling or intravenous cannulation were invited to consent to their infants’ participation in the study. Infants’ corrected ages were used as a criterion for eligibility, because it is thought that sucrose-induced analgesia may be associated with developmental changes related to age (Anseloni et al., 2002). It has been established that sucrose is effective in the neonatal population; therefore, possible confounding was reduced by ensuring that preterm infants older than 28 days were not included in the sample. The infants were stratified by corrected age into 29 days (>4 wk) to 12 weeks of age and those >12 weeks to 26 weeks of age. Every infant’s age was calculated by subtracting the number of weeks born before 40 weeks of gestation from the chronological age (Committee on Fetus and Newborn American Academy of Pediatrics, 2004). Infants were excluded if they were receiving nothing by mouth, receiving intravenous analgesia or sedation, fructose or sucrose intolerant, or had altered gag or swallow reflex, prior exposure to methadone (during the antenatal period), or where response to painful stimuli may be altered by a neuromuscular disease. Interventions Infants received 2 mL of either 25% sucrose or sterile water via syringe onto the anterior portion of the tongue over 30 seconds by the nurse caring for the infant. After administration of the oral solution, 2 minutes elapsed before commencing the procedure. Other than administration of the intervention, standard care was provided. Because the study hospital adhered to the principles of family-centered care and BabyFriendly Health Initiatives (1991), standard care included parents’ ability to be present or leave as they
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wished during the procedure, and the use of pacifiers occurred only with parental permission. They were offered by nurses present to those infants who normally used a pacifier and were crying. Venipunctures and heel lances were carried out by three competent children’s phlebotomists. Intravenous cannulations were done by resident doctors assigned to the ward. Infants were lying supine in their cot, swaddled, with the limb used for the painful procedure exposed, which was held by a phlebotomist not doing the procedure or the primary nurse caring for the infant, as consistent with standard care. Blinding and Randomization Infants were randomly assigned to receive an intervention of either sucrose or sterile water. Permuted block randomization was computer generated by the clinical trials pharmacist to ensure that roughly equal numbers of participants were allocated to each comparison group. The clinical trials pharmacist organized envelopes with the unique trial identification that appeared to be identical except for a sequential number on each. Once ascertained that an infant would have a painful procedure, the nurse opened the next envelope in sequence, which contained a syringe prepared by the pharmacists with either 2 mL of sucrose or 2 mL of sterile water. The codes remained unknown to anyone but the pharmacists until the trial was completed. The nurse who administered the intervention did not collect the data. Both data collectors were blinded to the intervention and were not involved in the care of the infants. Data Collection Pain was recorded using the Children’s and Infant’s Postoperative Pain Scale (CHIPPS) (Buttner & Finke, 2000). The scale ranges from 0 (no pain) to 10 (maximum pain) and measures the following five behavioral parameters of pain: crying, facial expression, posture of the trunk, posture of the legs, and motor restlessness (Table 1). CHIPPS has been reported as a reliable and valid tool for use in infants with internal consistency, interrater reliability, construct validity (Buttner & Finke), specificity, and sensitivity (Suraseranivongse, Kaosaard, Intakong, Pornsiriprasert, Karnchana, Kaopinpruck & Sangjeen, 2006) having been established. CHIPPS has been validated against the Neonatal Infant Pain Scale (Alves et al., 2008) and the Modified Behavioral Pain Scale (Buttner & Finke, 2000). An infant who is assumed to not have pain will score <4 points on CHIPPS, and a score of >3 points may be induced by pain or by other influences on the child’s comfort (Lindh et al., 2003).
TABLE 1. Children’s and Infant’s Postoperative Pain Scale (CHIPPS) Item Crying Facial expression Posture of the trunk Posture of the legs Motor restlessness
Structure
Points
None Moaning Screaming Relaxed/smiling Wry mouth Grimace (mouth and eyes) Neutral Variable Rearing up Neutral/released Kicking about Tightened legs None Moderate Restless
0 1 2 0 1 2 0 1 2 0 1 2 0 1 2
From ‘‘Analysis of behavioural and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young children: A comprehensive report on seven consecutive studies,’’ Buttner W. & Finke W. (2000), Paediatric Anaesthesia, 10(3), 315. Copyright 2000 by John Wiley and Sons. Reprinted with permission.
A baseline pain measurement was collected before the procedure and at the following points during the procedure: when the skin was swabbed, when the needle/lancet punctured the skin, and at blood draw or when the trocar was removed from the cannula. Completion of the procedure was denoted by cessation of handling by the phlebotomist or the doctor, at which point timing for postprocedure observations began. Postprocedure assessments occurred at 1, 2, and 3 minutes. If a second attempt of the procedure was required or if the procedure lasted for >5 minutes (7 minutes after administration of the intervention), the infant was excluded from the trial. Further observational data were collected at the same procedural and time points as pain scores and included the child’s disposition, occurrence of sucking, and whether comfort was being offered. Sucking included breastfeeding and nonnutritive sucking, such as use of a pacifier or sucking on a thumb or fist. Comfort was defined as any cuddling, patting, or verbal interaction between the infant and a parent, nurse, or other person. All infants admitted to the study ward who were likely to have a painful procedure were identified by the ward staff, and one of three registered nurses who were members of the research team was notified during study hours (weekdays, 07:00-18:00). The researcher screened the infant for eligibility and recruited infants. The study was explained to the family by the researcher, a parent information sheet was
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provided, and written consent was obtained. Information relating to medical history and infant’s age (actual and corrected) was recorded. Over the study period, data were collected by two nurses. Before commencement of the study, the nurses spent time in the clinical area to ensure that use of the tool was congruent with current practice. The interrater agreement for the nurses collecting data was found to have an intraclass correlation of 0.926 (p < .001; 95% confidence interval 0.8740.957). Data were recorded on a data collection sheet and entered into SPSS for Windows version 17.0.1 (Chicago, IL) by the principal researcher. Ethical Considerations Human Research Ethics Committee approval was granted by the study hospital. Participants’ parents were informed that they could choose not to have their infant participate in the study and it would not compromise the care of their child or their family and confidentiality was assured. Data Analysis Statistical Methods. Summary data were obtained for each treatment group by calculating means and SDs for continuous data and frequencies for categoric data. Demographic and other baseline variables were compared between treatment and placebo groups in each age group with the use of t tests or c2 tests as appropriate. Independent t tests were used to check for differences between time at each data collection point for each group. Because the distributions of pain scores were not normally distributed, Mann-Whitney tests were performed to compare the pain scores between groups at each data collection point for each group. Similarly, Mann-Whitney tests were performed to ascertain whether provision of nonnutritional sucking had an effect on pain scores. Independent t tests were used to ascertain differences between mean pain scores in infants who received sucrose and those who received water when ages were grouped (>4 weeks to 26 weeks of age, corrected) and to assess whether there was a difference in pain scores when nonnutritional sucking was provided compared with no sucking. A significance level of p ¼ .05 was used for all statistical tests. Sample Size. Sample size was based on the primary outcome of interest, the effect of sucrose on pain reduction. A reduction of 2 points was deemed to be clinically relevant. Based on earlier measurements of pain using a 10-point scale it was estimated that the SD of pain scores using CHIPPS was 2.2 (Bauer, Ketteler, Hellwig, Laurenz, & Versmold, 2004; Liu, Lin, Chou, & Lee, 2010). Assuming an alpha level of 0.05 and
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a power of 80%, a total sample of 20 infants was required to be able to detect a 2-point average difference on CHIPPS between two groups with the use of an independent t test (Power and Sample Size Program PS version 3.0.5).
RESULTS From August 2007 to January 2009, 111 infants were assessed for eligibility into the study, and 21 were excluded from this initial group (Fig. 1). Ninety infants were randomized to either the intervention or the control group. In age group 1 (>4-12 weeks), 22 infants were allocated and received sucrose, and 23 infants were allocated and 21 received water; in age group 2 (>12-26 weeks), 22 infants were allocated and 21 infants received sucrose, and 23 were allocated and received water. Three infants were unable to be included once recruited, because the researchers were unavailable when the procedures were being done. There were two adverse events that resulted in two infants being removed from the study. One, in age group 1, vomited after administration of the 2 mL sucrose, and the other, in group 2, coughed and gagged during administration of water, so administration was stopped. Both infants recovered spontaneously and the events were not deemed to be clinically significant. Data from another infant were removed from the analysis because the procedure lasted >7 minutes from the time intervention was administered. All remaining infants completed the study. Twenty-one received sucrose and 20 received water in the >4–12 weeks age range, and 21 and 22 received sucrose and water, respectively, in the >12–26-week age group. Figure 1 provides the study flow diagram. Comparison of demographic characteristics showed no significant differences between the two treatment groups. Provision of comfort by parent in group 2 at baseline, one and three minutes post procedure were significantly different (c2 ¼ 4.53; p ¼ .033; c2 ¼ 5.53; p ¼ 0.019; and c2 ¼ 4.56; p ¼ 0.033; respectively; Table 2). Time (in minutes and seconds) was calculated for each subsequent data collection point after intervention administration. No statistically significant differences were found in the times between sucrose and water groups in either age group nor between those who received nonnutritional sucking and those who did not. No statistical differences were found in pain scores between the intervention and control groups at any data collection point for either age group (Table 3). The infants aged >4-12 weeks that received sucrose had a lower median pain score at time of blood draw than those who had water (5, interquartile range
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Infants assessed for eligibility n = 111 Excluded (n=21) • Not meeting inclusion criteria (n=5) • Declined to participate (n=5) • Parents/researcher not available to seek consent (n=11) • Other reasons (n=0)
Eligible, consented, randomly assigned n = 90
Strata 1: >4 weeks-12 weeks n = 45
Allocated to sucrose n=22 • Received allocated intervention n=22 • Did not receive allocated n=0
Discontinued intervention (vomited) n=1
Analyzed n=21 • Excluded from analysis n=0
Strata 2: >12 weeks-26 weeks n = 45
Allocated to water n=23 • Received allocated intervention n=21 • Did not receive allocated intervention (researcher not available) n=2
Allocated to sucrose n=22 • Received allocated intervention n=21 • Did not receive allocated intervention (researcher not available) n=1
Discontinued intervention
Discontinued intervention
n=0
n=0
Analyzed n=20 • Excluded from analysis (procedure lasted > 7 min) n=1
FIGURE 1.
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[IQR] 6; and 7, IQR 7; respectively); similarly, the older group had a difference in median pain scores of 2 at time of needle insertion (5, IQR 6; and 7, IQR 5; respectively). Statistical differences in median pain scores were found between infants who did nonnutritional sucking and those who did not in age group 1 at 1 (z ¼ 2.83; p ¼ .005), 2 (z ¼ 2.00; p ¼ .045), and 3 minutes (z ¼ 2.10; p ¼ .036) after the procedure, with infants who did nonnutritional sucking having lower pain scores at each data collection point (Fig. 2). There were no statistical differences in times from intervention between all infants who had sucrose (n ¼ 42) compared with all infants who received water (n ¼ 42). There was a difference in pain scores at time of skin swab, with those who had water scoring higher than those who had sucrose (t ¼ 2.3; p ¼ .024). No other statistically significant differences were found (Fig. 3). The number of infants who used nonnutritional sucking at the various data collection points ranged from 36 to 50, with those who did not suck ranging from 33-48. Statistically significant differences in pain scores between infants who undertook
Allocated to water n=23 • Received allocated intervention n=23 • Did not receive allocated intervention n=0
Discontinued intervention (coughed & gagged) n=1
Analyzed n=21
Analyzed n=22
• Excluded from analysis n=0
• Excluded from analysis n=0
Flow diagram.
nonnutritional sucking and those who did not were found at 1 and 2 minutes after procedure (p values .043 and .027, respectively). Those provided with nonnutritional sucking recorded lower pain scores (Fig. 4).
DISCUSSION Results of this study show that infants undergoing venipuncture, intravenous cannulation, or heel lance procedures experience moderate to large pain (Blass & Shah, 1995; Boston Medical Center Pediatrics, 2010) with median pain scores as high as 7.5 (IQR 5) during skin penetration in infants >4-12 weeks old. Pain scores of 10 were recorded for ten infants during skin penetration by a needle, a further ten infants had pain scores of 9, and nine infants had pain scores of 10 during blood draw. The high pain scores recorded for this number of infants indicates that some type of analgesia needs to be used, particularly for infants who undergo painful procedures frequently. A strength of this study was the collection of pain scores during the minor procedures along with the actual time from administration of the intervention. The
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TABLE 2. Infants’ Characteristics Age Group 1, >4-12 wk Sucrose (n ¼ 21)
Age Group 2, >12-26 wk
Water (n ¼ 20)
Sucrose (n ¼ 21)
Water (n ¼ 22)
Mean (SD) Corrected age (wk) Actual age (wk) Weight (g)
7.7 (2.58) 9.4 (4.75) 4,569 (970)
7.2 (2.84) 8.1 (2.63) 4,384 (807)
17.1 (3.69) 18.4 (3.81) 5,917 (1519)
18.5 (4.40) 20.1 (4.38) 6,209 (1102)
n (%) Male gender Nonnutritional sucking* Comfort by parent* Minor painful procedure Venipuncture Heelprick IV cannulation Other Reason for admission Gastrointestinal Respiratory Neurological Infection/sepsis Cardiac Other
12 (57.1) 8-12 (38-57) 7-13 (33-62)
8 (40) 8-12 (40-60) 8-17 (40-85)
10 (47.6) 11-15 (52-74) 4-12 (19-57)†
16 (72.7) 9-14 (41-64) 11-19 (50-86)†
10 (47.6) 9 (42.9) 1 (4.8) 1 (4.8)
7 (35.0) 12 (60.0) 1 (5.0) 0
11 (52.4) 8 (38.1) 0 2 (9.5)
13 (59.1) 3 (13.6) 1 (4.5) 5 (22.7)
9 (42.9) 5 (23.8) 1 (4.8) 2 (9.5) 3 (14.3) 1 (4.8)
1 (5.0) 6 (30.0) 4 (20.0) 4 (20.0) 2 (10.0) 3 (15.0)
6 (28.6) 5 (23.8) 6 (28.6) 3 (14.3) 1 (4.8) 0
9 (40.9) 4 (18.2) 5 (22.7) 3 (13.6) 1 (4.5) 0
*Range of numbers provided, because the number of infants using a pacifier and receiving comfort from a parent varied at each data collection point. † p < .05 for comfort by parent for infants in stratum 2 between water and sucrose at baseline, 1 and 3 minutes post procedure
TABLE 3. Time from Intervention and Pain Scores for Interventions for Each Age Group Pain Score, Median (IQR) Time from Intervention (min:s), Mean (SD) Age Group 1: >4-12 wk corrected Baseline Skin swab Needle insertion Blood draw Completion of procedure 1 min after procedure 2 min after procedure 3 min after procedure Age Group 2: >12-26 wk corrected Baseline Skin swab Needle insertion Blood draw At completion of procedure 1 min after procedure 2 min after procedure 3 min after procedure
Sucrose
Water
p Value
2:04 (0:47) 2:45 (1:09) 4:18 (1:54) 5:54 (2:08) 6:54 (2:07) 7:54 (2:07) 8:54 (2:07)
0.0 (2) 1.0 (5) 7.0 (5) 5.0 (6) 5.0 (5) 1.5 (3) 1.0 (2) 0.0 (1)
0.0 (3) 3.0 (6) 7.5 (5) 7.0 (7) 5.0 (5) 3.0 (5) 0.0 (4) 0.0 (1)
.62 .25 .22 .31 .69 .36 .92 .95
2:36 (1:02) 3:14 (1:14) 4:33 (1:25) 5:53 (1:54) 6:56 (2:00) 7:53 (1:54) 8:57 (1:58)
0.0 (2) 1.0 (3) 5.0 (6) 5.0 (6) 4.0 (5) 1.0 (3) 1.0 (2) 1.0 (2)
1.0 (1) 2.5 (6) 7.0 (5) 6.0 (3) 3.5 (5) 2.0 (5) 1.0 (1) 0.0 (2)
.60 .13 .80 .69 .67 .33 .29 .83
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FIGURE 2. no pain.
Wilson et al.
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Pain scores for infants by nonnutritional sucking and age. *p < .05. Pain score #3 (below dashed line) signifies
FIGURE 3. - Pain scores for all infants by intervention. *p < .05. Pain score #3 (below dashed line) signifies no pain.
length of time from administration of intervention to needle penetration of the skin was an average 3 minutes 12 seconds, 4 minutes 41 seconds to blood draw, and 6 minutes 8 seconds to completion of the procedure. If it is accepted that the sucrose effect peaks at 2 minutes and lasts only 5-8 minutes (Buttner & Finke, 2000), the effects of sucrose would have been diminished when the blood was drawn. Nevertheless, the pain scores of infants who received sucrose were lower than those who received water in both groups at needle insertion and blood draw, although the differences were not statistically significant. Because the average time for the procedures was 3 minutes from needle insertion or 6 minutes from administration of the intervention, the effects of sucrose would have been minimal by the time the procedures were completed. This may explain why the pain scores were the same on completion of the procedure for infants that received water and sucrose in both age groups. A difference in pain scores was shown when data on all infants were analyzed together at the time the infants’ skin was swabbed. The mean pain score was 3.2
Oral Sucrose for Procedural Pain in Infants
FIGURE 4. - Pain scores for all infants by nonnutritional sucking. *p < .05. Pain score #3 (below dashed line) signifies no pain.
for those who received water. Although this score reflects an influence on the child’s comfort, an infant who does not have pain would score <4 (Dilli, Kucuk, & Dallar, 2009; Poulsen, 2009). The lower mean score (1.9) of those who had sucrose may represent the calming effect of sucrose to the cold stimulus of the alcohol skin swab at the 2-minute mark. The strength of sucrose used in this study was 25%, because this was the readily available stock strength provided by the pharmacy in the study hospital. Strengths of 24%-75% have been shown to be effective in reducing pain scores in infants during immunization, with mixed results when the lower strength of 12% was administered (Curtis et al., 2007). Increasing the strength of sucrose may not make any difference to behavioral pain scores in infants during painful procedures other than immunization, because 44% sucrose was not shown to reduce the pain score in a randomized controlled trial in infants aged 1-6 months during venipuncture; however, crying time was reduced (Buttner & Finke, 2000). Significant differences in pain scores were shown in group 1 between infants that received nonnutritional sucking and those who did not at 1, 2, and 3 minutes after the procedure. However, the median pain score was 3 at 1 minute after the procedure, which may indicate an alteration in comfort but does not signify pain (Curtis et al., 2007; Harrison et al., 2010). Similarly, a significant difference was found in mean pain scores
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when results for all infants were analyzed together, with those who did not suck having a higher pain score at 1 and 2 minutes after the procedure. Again, the highest mean pain score was 3.03 at 1 minute, which may indicate that infants who do not use a pacifier take longer to settle. Although not significant, nonnutritional sucking showed a difference of 2 points on the pain scale on completion of procedure in the younger infants and at blood draw in the older infants. As provision of a pacifier is a inexpensive intervention and has been shown to reduce crying time during venipuncture and immunizations (Reis et al., 2003); ensuring adherence to the BabyFriendly Health Initiative (1991) and parental wishes, this option should be considered when any painful procedure is being performed. Whether comfort was provided to the infants during the painful procedure was recorded. However, there were insufficient incidents of comfort by a parent to undertake meaningful analysis. Although the nurses and phlebotomists provided some comfort, actually cuddling the infant during the procedure was never done by staff or parents. Reis et al. (2003) found a combination of parental holding, oral tactile stimulation, and sucrose reduced crying time in infants during immunization. Although not recorded as part of the study, it was noted that parents often were not present when their infant was undergoing the procedure, which is consistent with the practice of family-centered care, where parents can stay or leave as they wish during procedures. Because age appeared to make no difference, the groups were combined and the larger sample of 84 infants was analyzed. Because the only statistically significant differences in pain scores were at data collection points when infants pain scores were <4, a reduction in infants’ settling is reflected rather than a reduction in pain. The nonsignificant differences in pain scores during the procedure add to the body of knowledge of the effectiveness of sucrose in reducing pain during minor procedures in infants 1-6 months old. Study Limitations The numbers in each group are similar to other studies that have shown an effect on behavioral pain scores between sucrose and water during venipuncture and heel lance in the neonatal population (Hatfield, 2008; Hatfield, Gusic, Dyer, & Polomano, 2008). Although the sample was sufficiently powered for the primary outcome, there were insufficient numbers for subgroup analyses to ascertain whether sucking or comfort had an effect on pain scores. The sample was a convenience sample with several potentially available infants being missed. The
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researchers were not available during the night nor over the weekends. As much demographic information was collected as possible on those infants that were missed, and there is nothing to suggest that they were different from the infants enrolled in the study. Randomization of intervention to those enrolled should have reduced any recruiting bias. The dose of sucrose was standardized for all infants and not based on the infant’s weight despite the infants’ weights ranging from 2,920 to 6,800 grams (group 1) and 3,315 to 9,700 grams (group 2). Studies that have based the dose of sucrose on infants’ weight have shown reductions in behavioral pain scores during immunizations (Blass & Shah, 1995). If the release of endogenous opioids is activated by the sweet taste (Duff, Louw, Loftus-Hills, & Morrell, 2001), then calculating the volume of sucrose based on an infant’s weight is unlikely to affect this mechanism. Clinical Implications While evidence is still unavailable of the effectiveness of oral sucrose during painful procedures other than immunizations, nurses should consider applying a topical anesthetic cream when there is time, because there is sufficient evidence to support its effectiveness in reducing pain in infants aged 1-6 months. When there is not time for the application of a topical anesthetic, because sucrose is inexpensive, readily available, and easy to use, and it lacks documented side effects, nurses may offer the hospital’s stock strength of oral sucrose for all painful procedures despite no clear evidence as to its effectiveness. However, three things should be considered: First, use oral sucrose in combination with a pacifier only with parental permission; second, consider beginning the procedure 1 minute after administration of sucrose so that the effect of sucrose, which peaks at 2 minutes, occurs when the
needle penetrates the infant’s skin; and third, consider administering 2 mL sucrose every 2 minutes until the procedure is completed to maintain the possible release of endogenous opioids. Further studies should try to ensure that the most painful part of the procedure occurs 2 minutes after administration of the sucrose or continue to provide sucrose every 2 minutes during the procedure to maximize the potential effects of sucrose. A composite pain tool that has been validated for use in the infant age group should be an outcome measure for all future research in this area.
CONCLUSION Infants do suffer pain when undergoing minor procedures. In this study there was insufficient evidence to show that 2 mL 25% oral sucrose administered 2 minutes before the onset of venipuncture, intravenous cannulation, or heel lance made a statistically significant difference to pain scores when measured with a validated behavioral pain scale in infants aged >412 weeks or >12-26 weeks corrected age. There were statistically significant differences in pain scores at 1, 2, and 3 minutes after the procedure for infants aged >4-12 weeks and at 1 and 2 minutes for all infants, with those undertaking nonnutritional sucking having lower pain scores at the 5% significance level. However, this probably reflects comfort and earlier settling, because the pain scores were <4 at each data collection point. Acknowledgments The researchers thank the families who agreed to participate, Margaret Shave and the clinical trials pharmacists, Jenni Corrigan and the phlebotomists and Tracey Maron and staff of the study ward.
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