oral sucrose and \"facilitated tucking\" for repeated pain relief in preterms: a...

$: Oral Sucrose and \"Facilitated Tucking\" for Repeated Pain Relief in Preterms: A Randomized Controlled Trial$
Oral Sucrose and “Facilitated Tucking” for RepeatedPain Relief in Preterms: A Randomized Controlled Trial

WHAT’S KNOWN ON THIS SUBJECT: Preterm infants are exposedto inadequately managed painful procedures during their NICUstay, which can lead to altered pain responses. Nonpharmacologicapproaches are established for the treatment of single painfulprocedures, but evidence for their effectiveness across time islacking.

WHAT THIS STUDY ADDS: Oral sucrose with or without the addedtechnique of facilitated tucking has a pain-relieving effect even inextremely premature infants undergoing repeated painexposures; facilitated tucking alone seems to be less effective forrepeated pain exposures over time.

abstractOBJECTIVES: To test the comparative effectiveness of 2 nonpharmaco-logic pain-relieving interventions administered alone or in combinationacross time for repeated heel sticks in preterm infants.

METHODS: A multicenter randomized controlled trial in 3 NICUs inSwitzerland compared the effectiveness of oral sucrose, facilitatedtucking (FT), and a combination of both interventions in preterm in-fants between 24 and 32 weeks of gestation. Data were collected duringthe first 14 days of their NICU stay. Three phases (baseline, heel stick,recovery) of 5 heel stick procedures were videotaped for each infant.Four independent experienced nurses blinded to the heel stick phaserated 1055 video sequences presented in random order by using theBernese Pain Scale for Neonates, a validated pain tool.

RESULTS: Seventy-one infants were included in the study. Interraterreliability was high for the total Bernese Pain Scale for Neonates score(Cronbach’s a: 0.90–0.95). FT alone was significantly less effective inrelieving repeated procedural pain (P , .002) than sucrose (0.2 mL/kg).FT in combination with sucrose seemed to have added value in therecovery phase with lower pain scores (P = .003) compared with boththe single-treatment groups. There were no significant differences in painresponses across gestational ages.

CONCLUSIONS: Sucrose with and without FT had pain-relieving effectseven in preterm infants of ,32 weeks of gestation having repeatedpain exposures. These interventions remained effective during repeatedheel sticks across time. FT was not as effective and cannot berecommended as a nonpharmacologic pain relief intervention forrepeated pain exposure. Pediatrics 2012;129:299–308

AUTHORS: Eva L. Cignacco, PhD, RM,a Gila Sellam, MSN,RN,a Lillian Stoffel, BSN, RN,b Roland Gerull, MD,b MathiasNelle, MD,b Kanwaljeet J. S. Anand, Prof, MBBS, DPhil,c andSandra Engberg, Prof, PhD, CRNP, FAANa,d

aInstitute of Nursing Science, University of Basel, Basel,Switzerland; bDivision of Neonatology, Children’s Hospital,University Hospital Bern, Bern, Switzerland; cPediatric CriticalCare Medicine, Le Bonheur Children’s Hospital, University ofTennessee Health Science Center, Memphis, Tennessee; anddSchool of Nursing, University of Pittsburgh, Pittsburgh,Pennsylvania

KEY WORDSinfant premature, pain, analgesia, nonpharmacologic pain relief,sucrose, facilitated tucking

ABBREVIATIONSBPSN—Bernese Pain Scale for NeonatesB-BPSN—behavioral Bernese Pain Scale for Neonates scoreFT—facilitated tuckingGA—gestational ageNPI—nonpharmacologic interventionP-BPSN—physiological Bernese Pain Scale for Neonates scoreT-BPSN—total Bernese Pain Scale for Neonates score

Dr Cignacco, primary investigator, was responsible fordevelopment of study design and organization of the study, datacollection, supervision of doctoral student in all the empiricalsteps, and manuscript draft and revision. Ms Sellam, doctoralstudent, was responsible for data collection, data entry andquality check, data analysis, and manuscript draft and revision.Ms Stoffel and Dr Gerull were responsible for data collection,manuscript revision, and critical review. Dr Nelle, coinvestigator,was responsible for manuscript revision and critical review. DrAnand, research funding advisor, was responsible fordevelopment of the study design, manuscript revision, andcritical review. Dr Engberg, methodological advisor, wasresponsible for development of the study design, reviews of dataanalysis, manuscript revision, and critical review.

www.pediatrics.org/cgi/doi/10.1542/peds.2011-1879

doi:10.1542/peds.2011-1879

Accepted for publication Sep 28, 2011

Address correspondence to Eva L. Cignacco, PhD, RM,Bernoullistrasse 28, CH-4056 Basel, Switzerland. E-mail: [email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

PEDIATRICS Volume 129, Number 2, February 2012 299

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The survival of preterm infants is de-pendentonhighlysophisticatedintensivecare, associatedwith an exceedingly highnumber of painful procedures.1 This isparticularly true for infants with ex-tremely low gestational ages (GAs) whoalso receive less analgesia.2–5

Repeated pain exposures during criti-cal windows of central nervous systemdevelopment6,7 are associated withpermanent changes in peripheral, spi-nal, and supraspinal pain processing;neuroendocrine function; and neuro-logic development. These changes canbe manifested by alterations in painthresholds, stress responses, cogni-tive function, behavioral disorders,and long-term disabilities.7,8 Despitethis knowledge, many painful proce-dures in NICUs are performed withoutpharmacologic or nonpharmacologicanalgesia.1–3,9 Disadvantages of phar-macologic analgesia include side effects,questionable efficacy, and possible neg-ative impact on neonatal outcomes.10–12

As an alternative approach, nonpharma-cologic interventions (NPIs) are recom-mended for pain management.13–15

NPIs (eg, oral sucrose, breastfeeding,non-nutritive sucking, facilitated tuck-ing [FT], kangaroo care, swaddling)effectively reduce pain for minor tomoderately painful procedures.15–17

They promote self-regulation of the infantand provide oro-tactile, oro-gustatory,and tactile stimulation, capable of re-ducing infants’ pain responses duringmost painful procedures.15,18–21 Sucroseis recommended extensively for painrelief in preterm infants22–24 and hasshown to be highly effective and safe forsingle procedures by Stevens et al.17

Sweet taste solutions seem to triggerendogenous opioid and nonopioid path-ways.25,26 FT is described as holding theinfant by placing a hand on his or herhands and feet and by positioning theinfant in a flexed midline position whilein either a side-lying, supine, or proneposition.27,28 This technique provides the

infant with support and the chance tocontrol his or her own body.16 Severalstudies reported that FT stabilizes be-havioral and physiologic states duringsingle heel sticks and endotrachealsuctioning, reducing the infant’s stressin coping with pain.16,27–31

Althoughcurrent evidencesupports theeffectiveness of NPIs for a single painfulprocedure, there is little research ex-amining their effectiveness across re-peated painful procedures. To date, fewstudies have evaluated the effective-ness of sucrose over time,32–36 andnone have evaluated FT across time.The combination of 2 NPIs (eg, oralsucrose and FT) may have additiveeffects by stimulating infants in a multi-sensorial way to cope with the painfulexperience.18,37,38

This study compared the impact ofsucrose and FT alone and in combina-tion on pain reactivity across multiplepainful procedures. Randomized groupsreceived oral sucrose, FT, and a combi-nation of both strategies to evaluatepossible additive effects. The primaryoutcome was pain response measuredby the Bernese Pain Scale for Neonates(BPSN) total and component scores. Thesecondary outcome was the impact ofgestationalgroup(240/7 to276/7and280/7 to 32 0/7 gestational weeks) on theeffectiveness of these interventions.

METHODS

Setting and Sample

This randomized controlled trial wascarried out in NICUs of 3 universityhospitals in Switzerland from January12 to December 31, 2009. Infants ad-mitted to the NICU during this periodwere assessed for eligibility accordingto the following inclusion criteria: bornbetween 24 0/7 and 32 0/7 weeks ofgestation and anticipated clinical needfor at least 5 routine capillary bloodsamples within 2 weeks after birth.Infantswere excluded if they had severe

intraventricularhemorrhage(grades IIIand IV), had life-threatening malforma-tions or disorders affecting brain circu-lation or the cardiovascular system, hadundergone a surgical procedure, hada pH ,7.00, or had any problem thatcould impair pain expression.

Sample Size Calculation

By using sucrose only, we performeda feasibility study to calculate a pre-liminary power analysis.39 We formu-lated our calculations based on theassumptions that sucrose and FTwouldhave equivalent effects that wouldsustain over time. According to thisanalysis, a group size of n = 24 for eachintervention group (n = 72 total samplesize) provided adequate power to detecta pain reduction of 33% for the combi-nation group relative to the 2 single in-tervention groups with a power of 80%.

Data Collection and Management

Data were collected during 5 noncon-secutive routine heel sticks (T1–T5) be-tween postnatal days 2 and 16, with thefirst heel stick performed no later thanday 4. For other painful procedures in-cluding heel sticks where data werenot being collected, the infants wereprovided with sucrose 20%, whichwas the standard of care in all partici-pating NICUs. Because the timing ofblood sampling was determined byclinical considerations, there were nofixed time points for data collection.Demographic data were collected frommedical records.

Data collection occurred during (1)baseline (before any manipulation), (2)heel stick (skin preparation, heel stick,and hemostasis after bloodwas drawn),and (3) recovery (3 minutes after theheel stick).Most heel sticks took place inthe morning and each infant was un-disturbed for at least 30 minutes beforedata collection. Phases were videotaped(Panasonic high-definition camcorder,model HDC-HS9, Osaka, Japan) for at

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least 3 minutes by a trained study nurseby using a standardized procedure. Norecording occurred during heel warm-ing (2–3 minutes) between the first andsecond phases. The infant’s nurse per-formed the heel stick. Sucrose was ad-ministrated by the nurse, whereas theFTwas performed by a second nurse ortrained study nurse. The exact time ofthe videotaping of each phase wasdocumented, as well as the duration ofheel sticks. Fifteen videotape seg-ments were produced per infant (3sequences per procedure 3 5 heelsticks = a total of 1065 video sequen-ces for the study).

Each video segment was checked forquality and digitally edited by trainedstudy nurses by using the Final CutExpress software (version 4.0.1. 2002–2008 Apple Inc, Cupertino, CA) to elim-inate any information that would haveindicated the heel stick phase. Videorecordings of poor quality were dis-carded (n = 10). The final sample of 1055sequences was assigned in randomorder in relation to the number (T1–T5)and the phase (baseline, heel stick, re-covery) of the heel stick being recorded.All digital records were provided to 4nurses for assessment of pain responsesduring each sequence. The videotapingprocedure was designed to ensurethat the raters could not see if the heelstick procedure was being performed.

The NPI groups were (1) oral sucrose20% (0.2 mL/kg), (2) FT, and (3) a com-bination of both interventions. Sucrosewas administrated orally ∼2 minutesbefore the heel stick. If the infantseemed to be in pain during the heelstick phase, up to 2 additional doses ofsucrose were administrated and notedin the study chart. FTwas started at thebeginning of the baseline phase, andthe infant was “tucked” through all 3phases. In the combination group, theFT was started at the beginning of thebaseline phase and sucrose was given2 minutes before the heel stick.

Variables and Measures

Information about GA, method of de-livery, gender, parity, birthweight, Apgarscores, mechanical ventilation or con-tinuous positive airway pressure duringthe heel stick, and number of painfulprocedures each day was collected.

Pain response, the dependent variable,was measured by using the BPSN totaland component scores. The BPSN con-tains 9 items: 3 physiologic (heart rate,respiratory rate, and oxygen satura-tion) and 6 behavioral (grimacing, bodymovements, crying, skin color, sleepingpatterns,consolation) items.Physiologicdata (heart rate and oxygen saturation)synchronized with the 3 phases of datacollection were downloaded from theclinical monitoring database for theBPSN. Raters counted the breathing ratewhile viewing the video sequences.Raters scored behavioral items andbreathing only; heart rate and oxygensaturation were scored by using physi-ologic data collected during each phase.Each item was scored on a 3-point scale(0–3 points). Higher scores for thebehavioral items and greater changesin the physiologic items indicated in-creased pain, whereas a total scoreof #11 was considered nonpainful.40

The neonatal nursing experts whorated the video sequences attended astandardized instruction session abouthow to perform the rating and theyrated the sequences independently.

Initial psychometric testing of the BPSNdemonstrated good construct validitywith differentiation between painfuland nonpainful procedures (F = 41.27,P # .0001) and intrarater and inter-rater reliability correlation coefficientsof r = 0.98 to 0.99 and r = 0.86 to 0.97,respectively. In a recent revalidation ofthe BPSN, a cutoff score of #11 wasconsidered nonpainful (sensitivity of100.0% and specificity of 89.4%).41 Forthis study, 3 BPSN scoreswere calculated:the total (T-BPSN), behavioral (B-BPSN),and physiologic (P-BPSN) BPSN scores.

Interrater Agreement

Interrater reliability for the T-BPSNscores in this study averaged 99.2%for the 5 heel sticks (range: 98.8% forheel stick 1 and 99.8% for heel stick 5).Because the interrater reliability wasvery high, we used the average raters’BPSN scores within infants over time (5heel sticks). Within-infant variability inT-BPSN scores across time was high(86.3%, P, .0001). Interrater reliabilityfor B-BPSN scoreswas 98.8%. Interraterreliability, measured by Cronbach’s a

coefficient, ranged between 0.90 and 0.95for the different phases.

Randomization

To ensure equal balance of the in-tervention group per site, block ran-domization by using SPSS, version 16(SPSS Inc, Chicago, IL) was performed.For each site, 8 infants were randomlyallocated to each of the 3 interventions(24 infants per site, and 24 infants perintervention group for the entire studysample). For each site, group assign-mentsweresealed in opaqueenvelopesand consecutively numbered. Whenparents consented to participation, theenvelope was opened by a study nurseandthe interventiongroupwasrevealed.Envelopes were prepared by a studynurse not involved in the data collectionprocess.

During the study period, 201 infants of,32 weeks of gestation were assessedfor eligibility to participate in the study.In each site, a study nurse called thereferring NICU daily and asked if anynew infants were eligible to participatein the study.

Ethical Consideration

The study was approved by the ethicalboards of the Cantons of Basel, Bern,and Zürich. Written informed consentwas obtained from a parent. The studydesign did not include a no-interventioncontrol group based on the evidencethat exposure of preterm infants to

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pain procedures without treatmentis harmful.14

Data Analysis Procedures

All data were analyzed by using IBMSPSS statistics software (version 19)and SAS (version 9.1) (SAS Institute, Inc,Cary, NC). Data entry quality was con-trolled by double-entry procedures andan error rate of ,1% was detected.Descriptive statistics were used to de-scribe the demographic and medicalcharacteristics of the infants, whereasthe x2 test and Kruskal–Wallis or Mann–Whitney U tests were used for compar-isons among the 3 intervention groups

and between the 2 GA groups. The meannumber of painful procedures was com-pared per site per infant per day, by us-ing 1-way analysis of variance and posthoc Tukey test. Correlations betweenphysiologic and behavioral items of theBPSN were calculated with the Pearsoncoefficient. Clinical site, GA group, num-ber of painful procedures, and heel stickduration were examined as possibleconfounders on the impact of the NPIson BPSN scores; none had a confoundeffect. The primary hypothesiswas testedby using a repeated measures analysis.We used a random slopes regressionmodel, which allowed each subject to

have his or her own regression over the5 heel sticks. Because of high interraterreliability, scores of the 4 raters wereaveraged and transformed logarithmi-cally to satisfy the assumptionof normallydistributed residuals. For comparisonsamong the 3 phases, scores across the5 heel stickswere also averaged. Ana of0.05 was considered significant.

RESULTS

Sample Characteristics andNumber of Daily Procedures

Seventy-one infantswereenrolled in thestudy and all but 1 had complete data.

FIGURE 1Flow diagram of the recruitment and randomization process.


The fifth heel stick was missed for 1infant. Figure 1 presents the flow dia-gram of the recruitment and random-ization process based the ConsolidatedStandards of Reporting Trials guide-lines.42 The mean GA of the participat-ing infants at birth was 29.2 (SD61.8)weeks, mean birth weight was 1174 g(SD6337), andmean number of painfulprocedures during 0 to 14 days was 201(SD 6104). Sample characteristics aresummarized in Table 1.

Testing the Effectivenessof the NPIs

We compared the effectiveness of su-crose, FT, and their combination in re-ducing pain responses during heel stickprocedures. Table 2 presents the meanscores of the T-BPSN, B-BPSN, and P-BPSNscores for the 3 intervention groups. Thecorrelation between the infants’ meanbehavioral and physiologic pain scoresacross the raters and phases of the heel

stick was low (r = 0.19). Effectiveness ofthe interventions was examined by

comparingmean pain responses over allheel sticks. Figure 2 presents the mean

behavioral and physiologic pain scores

over all 5 heel sticks as predicted by theregression analysis. During heel stick

phase, the FT group had significantly

higher B-BPSN (P = .01; .007) and P-BPSN(P = .0002; .003) scores than the sucrose

and combination groups. During therecovery phase, there were no signifi-cant differences in P-BPSN scores, butthe combination group had significantlylower B-BPSN scores than both theother groups (P = .006; .008).

Figure 3 shows how the B-BPSN andP-BPSN of heel stick phase scores foreach group changes across the 5 heelsticks. P-BPSN scores for the FT group

TABLE 1 Demographic and Medical Characteristics of the Sample

Total Sample NPI Group

Sucrose FT Combinationn (%) n (%) n (%) n (%) P, x2

Sample 71 (100) 24 (33.8) 24 (33.8) 23 (32.4) .986Gender .983

Female 32 (45.0) 11 (45.8) 11 (45.8) 10 (43.5)Male 39 (55.0) 13 (54.2) 13 (54.2) 13 (56.5)

Way of delivery .805Normal birth 6 (8.5) 3 (12.5) 1 (4.2) 2.(8.7)Planned cesarean delivery 16 (22.5) 4 (16.7) 6 (25.0) 6 (26.1)Emergency cesarean delivery 49 (69.0) 17 (70.8) 17 (70.8) 15 (65.2)

Number of birth .462Single 50 (70.4) 19 (79.2) 14 (58.3) 17 (73.9)One of twins 14 (19.7) 3 (12.5) 8 (33.3) 3 (13.0)One of triplet 5 (7.0) 2 (8.3) 1 (4.2) 2 (8.7)One of quadruplet 2 (2.8) 0 (0) 1 (4.2) 1 (4.3)

Mean (SD) Mean (SD) Mean (SD) Mean (SD) P, Kruskal-WallisGA at birth, wk and d 29.24 (1.8) 28.95 (1.7) 29.20 (1.7) 29.5 (2) .389Duration of HS, min HS 1 5.04 (5.2) 4.38 (3.8) 4.12 (3.6) 6.7 (7.4) .687

HS 2 4.75 (4.3) 4.54 (4.5) 4.67 (3.5) 5.04 (5.0) .851HS 3 5.01 (4.8) 4.46 (3.1) 4.95 (4.7) 5.65 (6.2) .878HS 4 4.73 (3.7) 5 (3.9) 5.33 (4.0) 3.83 (3) .305HS 5 4.77 (3.6) 4.65 (3.7) 5.38 (4.1) 4.26 (2.9) .751

Birth weight, g 1174.44 (337) 1080 (286) 1228 (397) 1217 (309) .308Apgar scores 1 min 5.97 (2.1) 5.65 (2.3) 5.46 (2.3) 6.83 (1.6) .070

5 min 7.58 (1.6) 7.21 (1.4) 7.29 (1.8) 8.26 (1.2) .030a

No. of painful procedures per day 14.38 (7.4) 15 (10) 15 (9) 13 (9) .012a

No. of HSs per infants per day 1.07 (1.2) 1 (1) 1 (1) 1 (1) .539

HS, heel stick.a The significance level is .05.

TABLE 2 Mean Pain Scores for All Raters Across All Heel Sticks Measured by the BPSN

NPI Group

Sucrose FT Combination

Score Phase Mean SD Mean SD Mean SD

T-BPSN Baseline 4.03 2.08 4.99 3.24 4.62 2.88Heel stick 7.48 3.64 9.75 4.73 7.53 3.75Recovery 4.87 2.04 5.18 2.87 4.23 2.68

B-BPSN Baseline 4.02 2.08 4.97 3.25 4.62 2.88Heel stick 5.58 2.95 7.01 3.59 5.49 2.95Recovery 3.66 1.71 3.90 2.47 3.18 2.24

P-BPSN Baseline 0 0 0.04 0.22 0 0.03Heel stick 1.89 1.79 2.72 1.98 2.03 1.73Recovery 1.23 1.35 1.28 1.31 1.05 1.23

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increased significantly from heel stick1 to 5 (P = .01), whereas there were nosignificant changes for the sucrose(P = .08) and combination (P = .43)groups. Overall, B-BPSN scores showedno significant changes over time, butthe slope between heel stick 1 and 2decreased significantly (P = .01) for theFT group and the slope between heelstick 4 and 5 increased significantly(P = .03) for the sucrose group.

In the sucrose and combination groups(n = 47), 21 infants (44.7%) receivedadditional doses of sucrose. Duringheel stick phase, infants who receivedadditional doses of sucrose had sig-nificantly higher B-BPSN scores thanthose who did not receive additionaldoses (P = .02), whereas their P-BPSNscores were not significantly different(P = .50). There were no significantdifferences in the recovery phase

behavioral (P = .85) or physiologic (P =.26) pain scores of infants who didor did not receive additional doses ofsucrose.

DISCUSSION

The findings of this study show thateither sucrose alone or sucrose incombination with FT remains effectiveacross 5 heel sticks in preterm infants

FIGURE 2Slope testing NPI groups and phases.


of,32 weeks of gestation, whereas FTalone appears to be less effective.Furthermore, the results indicate thatthe combination of sucrose and FT mayhave additive pain-relieving effectsduring the recovery phase.

Our findings are consistent with pre-vious studies regarding the efficacyof sucrose over time.32–35 No sign oftolerance to the analgesic effects of

sucrose was observed. It is importantto note that FT was not lacking efficacybut rather was less effective than the 2other interventions. The mean T-BPSNand B-BPSN scores during all phaseswere ,10 points, even for infants inthe FT group. Previous data suggestthat a T-BPSN score #11 points or aB-BPSN score ,8 points is consideredas “no pain.” The efficacy of FT has been

described in several studies,16,27–29,43

although these studies did not com-pare FTwith other NPIs. Our study is thefirst to compare the efficacy of FT orsucrose across time with its efficacywhen used in combinationwith sucrose.

Infants in the sucrose and combinationgroups who received additional dosesof sucrose had significantly higherbehavioral pain scores across all 5 heel

FIGURE 2(Continued)

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sticks. Regardless of these findings,there were no differences in recoveryphase between infants who did or didnot receive additional doses of sucrose.Our findings correspond to those ofJohnston et al,44 who examined theeffects of repeated doses of sucrose inpreterm infants receiving sucrose so-lution or sterile water either 2 minutesbefore, just before, or 2 minutes after

the heel stick. Their results showedthat repeated doses of sucrose, at2-minute intervals, increases the an-algesic effect in preterm infants.

Another previous randomized trial ques-tions the analgesic efficacy of sucrose,based on EEG and electromyogramrecordings in healthy term newborns(37–43 weeks), receiving sucrose orsterile water 2 minutes before a heel

stick. Slater et al45 found no differ-ences in nociceptive brain activity orin the magnitude or latency of thespinal nociceptive reflexes after theheel stick, between infants who re-ceived sucrose and those who receivedwater, although Premature Infant PainProfile scores and pain-related facialexpressions were significantly re-duced in the sucrose-treated infants.These findings contradict data froma large body of literature supportingthe analgesic efficacy of sucrose orother sweet solutions. Moreover, thereare several methodological concernsrelated to the Slater et al study45 thatmake it seem premature to concludethat sucrose is ineffective based onlyon its findings.46

Although the differences between thesucrose and combination groups inbehavioral and physiologic scoresduring the recovery phase were sta-tistically significant, the magnitudeof these differences is probably notclinically meaningful. This poses a criti-cal question related to the cost-effectiveness of this intervention. FT isa time-consuming intervention, whichcouldbeusedasaprocedure toenhanceparenting or bonding, but needs to bequestioned as a nursing intervention.Although there are promising find-ings regarding FT as an effective NPI,30

the challenges of this specific in-tervention in nursing practice needto be reconsidered in an environ-ment characterized by economic con-straints.47

The methodological strengths of thisstudy are the strategies undertaken toenhance the internal validity of theseresults. The use of 4 trained and ex-perienced nurses to perform painassessment, the randomization ofthe sequences to blind the raters tothe phase of the procedure, and thethorough elaboration of each singlevideo sequence reduced potentialbiases.

Heel stick

FIGURE 3Pain scores over the heel sticks for phase 2 (heel stick) measured by the BPSN.

Heel stick

FIGURE 3(Continued)


There are some methodological limi-tations in thisstudy,however. Theraterscould be only partially blinded to theNPI group because the clear visibility ofthe FT procedure could cause possiblebias. Nevertheless, raters did not knowif the infant was in the FT-only groupor in the combination group. A furtherlimitation was the exclusion of a no-intervention control group owing toethical considerations. Long-term conse-quences of repeated doses of sucrosewere investigated in a small numberof studies, but there are no conclusivefindings regarding the risk for poorneurologic outcomes. In the currentstudy, we did not follow infants for neu-rologic outcomes. Further research re-garding consequences of prolongeduse of sucrose is needed. Another limi-tation of this study was that although theoriginal protocol was for infants in theFT-only group to receive FT for all painfulprocedures during the time they wereenrolled in the study, staff shortagesmade it impossible for nurses to im-plement this procedure consistently fornonstudy painful procedures.47 Conse-quently, these infants were treated with

oral sucrose 20% (the standard of carein the units) for nonstudy procedures.The impact that this had on the efficacyof FTalone is unknown but it is possiblethat consistent use of this proceduremay have altered its efficacy.

CONCLUSIONS

The results of this randomized con-trolled trial provide evidence that oralsucrose alone or combined with FTremains effective in reducingheel stick-related pain over time in preterminfants (24–32 weeks), during the crit-ical phase of the first 14 days of NICUstay. These findings have importantclinical implications for the manage-ment of pain in preterm infants of lowGA, who are at risk for a high frequencyof painful procedures during their NICUstay. During the recovery phase of theheel stick, the combination of FT andoral sucrose was slightly more effectivein reducing pain than sucrose alone.This difference was not, however, clini-cally meaningful, particularly given theadditional resources needed to imple-ment the combined intervention.

ACKNOWLEDGMENTSWe acknowledge the financial contri-bution of the Swiss National ScienceFoundation and the following privatefoundations: Botnar Foundation, Basel;the Foundation of Nursing Science,Basel; the Foundation for Research inNeonatology, Zürich; the Marie Anna-Foundation, Basel; and the Foundationfor Sick Children, Basel.

We are grateful to all parents who con-sented to include their preterm infantinto the study. We thank all the nurses,head nurses, and medical directors ofthe Children’s University Hospital, Basel,Bern, and Zürich, for their efforts tomake this study possible. We would fur-ther like to thank the New Media Centreteam of the University of Basel for theexcellent and professional support inthe video-data elaboration process andsupervision of research assistants. Wealso thank Dr Kris Denhaerynck forthe professional statistical support.Finally, this research would not havebeen feasible without the help of stu-dents and research assistants of theInstitute of Nursing Science of the Uni-versity of Basel.

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DOI: 10.1542/peds.2011-1879; originally published online January 9, 2012; 2012;129;299Pediatrics

Kanwaljeet J. S. Anand and Sandra EngbergEva L. Cignacco, Gila Sellam, Lillian Stoffel, Roland Gerull, Mathias Nelle,

Randomized Controlled TrialOral Sucrose and ''Facilitated Tucking'' for Repeated Pain Relief in Preterms: A

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DOI: 10.1542/peds.2011-1879; originally published online January 9, 2012; 2012;129;299Pediatrics

Kanwaljeet J. S. Anand and Sandra EngbergEva L. Cignacco, Gila Sellam, Lillian Stoffel, Roland Gerull, Mathias Nelle,

Randomized Controlled TrialOral Sucrose and ''Facilitated Tucking'' for Repeated Pain Relief in Preterms: A

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