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Published in: BMC Pediatrics 1/2018

Open Access 01-12-2018 | Research article

The minimally effective dose of sucrose for procedural pain relief in neonates: a randomized controlled trial

Authors: Bonnie Stevens, Janet Yamada, Marsha Campbell-Yeo, Sharyn Gibbins, Denise Harrison, Kimberley Dionne, Anna Taddio, Carol McNair, Andrew Willan, Marilyn Ballantyne, Kimberley Widger, Souraya Sidani, Carole Estabrooks, Anne Synnes, Janet Squires, Charles Victor, Shirine Riahi

Published in: BMC Pediatrics | Issue 1/2018

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Abstract

Background

Orally administered sucrose is effective and safe in reducing pain intensity during single, tissue-damaging procedures in neonates, and is commonly recommended in neonatal pain guidelines. However, there is wide variability in sucrose doses examined in research, and more than a 20-fold variation across neonatal care settings. The aim of this study was to determine the minimally effective dose of 24% sucrose for reducing pain in hospitalized neonates undergoing a single skin-breaking heel lance procedure.

Methods

A total of 245 neonates from 4 Canadian tertiary neonatal intensive care units (NICUs), born between 24 and 42 weeks gestational age (GA), were prospectively randomized to receive one of three doses of 24% sucrose, plus non-nutritive sucking/pacifier, 2 min before a routine heel lance: 0.1 ml (Group 1; n = 81), 0.5 ml (Group 2; n = 81), or 1.0 ml (Group 3; n = 83). The primary outcome was pain intensity measured at 30 and 60 s following the heel lance, using the Premature Infant Pain Profile-Revised (PIPP-R). The secondary outcome was the incidence of adverse events. Analysis of covariance models, adjusting for GA and study site examined between group differences in pain intensity across intervention groups.

Results

There was no difference in mean pain intensity PIPP-R scores between treatment groups at 30 s (P = .97) and 60 s (P = .93); however, pain was not fully eliminated during the heel lance procedure. There were 5 reported adverse events among 5/245 (2.0%) neonates, with no significant differences in the proportion of events by sucrose dose (P = .62). All events resolved spontaneously without medical intervention.

Conclusions

The minimally effective dose of 24% sucrose required to treat pain associated with a single heel lance in neonates was 0.1 ml. Further evaluation regarding the sustained effectiveness of this dose in reducing pain intensity in neonates for repeated painful procedures is warranted.

Trial registration

ClinicalTrials.​gov: NCT02134873. Date: May 5, 2014 (retrospectively registered).
Literature
1.
go back to reference Bueno M, Yamada J, Harrison D, Khan S, Ohlsson A, Adams-Webber T, et al. A systematic review and meta-analyses of nonsucrose sweet solutions for pain relief in neonates. Pain Res Manage. 2013;18(3):153–61.CrossRef Bueno M, Yamada J, Harrison D, Khan S, Ohlsson A, Adams-Webber T, et al. A systematic review and meta-analyses of nonsucrose sweet solutions for pain relief in neonates. Pain Res Manage. 2013;18(3):153–61.CrossRef
2.
go back to reference Stevens B, Yamada J, Ohlsson A, Haliburton S, Shorkey A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2016;7(7):CD001069.PubMed Stevens B, Yamada J, Ohlsson A, Haliburton S, Shorkey A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2016;7(7):CD001069.PubMed
3.
go back to reference Lee GY, Yamada J, Kyololo O, Shorkey A, Stevens B. Pediatric clinical practice guidelines for acute procedural pain: a systematic review. Pediatrics. 2014;133(3):500–15.CrossRefPubMed Lee GY, Yamada J, Kyololo O, Shorkey A, Stevens B. Pediatric clinical practice guidelines for acute procedural pain: a systematic review. Pediatrics. 2014;133(3):500–15.CrossRefPubMed
4.
go back to reference Taddio A, Yiu A, Smith RW, Katz J, McNair C, Shah V. Variability in clinical practice guidelines for sweetening agents in newborn infants undergoing painful procedures. Clin J Pain. 2009;25(2):153–5.CrossRefPubMed Taddio A, Yiu A, Smith RW, Katz J, McNair C, Shah V. Variability in clinical practice guidelines for sweetening agents in newborn infants undergoing painful procedures. Clin J Pain. 2009;25(2):153–5.CrossRefPubMed
5.
go back to reference Bellieni CV, Johnston CC. Analgesia, nil or placebo to babies, in trials that test new analgesic treatments for procedural pain. Acta Paediatr. 2016;105(2):129–36.CrossRefPubMed Bellieni CV, Johnston CC. Analgesia, nil or placebo to babies, in trials that test new analgesic treatments for procedural pain. Acta Paediatr. 2016;105(2):129–36.CrossRefPubMed
6.
go back to reference Campbell-Yeo M. ‘First, do no harm’--the use of analgesia or placebo as control for babies in painful clinical trials. Acta Paediatr. 2016;105(2):119–20.CrossRefPubMed Campbell-Yeo M. ‘First, do no harm’--the use of analgesia or placebo as control for babies in painful clinical trials. Acta Paediatr. 2016;105(2):119–20.CrossRefPubMed
7.
go back to reference Harrison D, Bueno M, Yamada J, Adams-Webber T, Stevens B. Analgesic effects of sweet-tasting solutions for infants: current state of equipoise. Pediatrics. 2010;126(5):894–902.CrossRefPubMed Harrison D, Bueno M, Yamada J, Adams-Webber T, Stevens B. Analgesic effects of sweet-tasting solutions for infants: current state of equipoise. Pediatrics. 2010;126(5):894–902.CrossRefPubMed
9.
go back to reference Stevens B, Johnston C, Franck L, Petryshen P, Jack A, Foster G. The efficacy of developmentally sensitive interventions and sucrose for relieving procedural pain in very low birth weight neonates. Nurs Res. 1999;48(1):35–43.CrossRefPubMed Stevens B, Johnston C, Franck L, Petryshen P, Jack A, Foster G. The efficacy of developmentally sensitive interventions and sucrose for relieving procedural pain in very low birth weight neonates. Nurs Res. 1999;48(1):35–43.CrossRefPubMed
10.
go back to reference Blass EM, Shide DJ. Some comparisons among the calming and pain-relieving effects of sucrose, glucose, fructose and lactose in infant rats. Chem Senses. 1994;19(3):239–49.CrossRefPubMed Blass EM, Shide DJ. Some comparisons among the calming and pain-relieving effects of sucrose, glucose, fructose and lactose in infant rats. Chem Senses. 1994;19(3):239–49.CrossRefPubMed
11.
go back to reference Pillai Riddell RR, Racine NM, Gennis HG, Turcotte K, Uman LS, Horton RE, et al. Non-pharmacological management of infant and young child procedural pain. Cochrane Database Syst Rev. 2015;(12):Cd006275. Pillai Riddell RR, Racine NM, Gennis HG, Turcotte K, Uman LS, Horton RE, et al. Non-pharmacological management of infant and young child procedural pain. Cochrane Database Syst Rev. 2015;(12):Cd006275.
12.
go back to reference Ohlsson A, Shah PS. Paracetamol (acetaminophen) for prevention or treatment of pain in newborns. Cochrane Database Syst Rev. 2015;(6):Cd011219. Ohlsson A, Shah PS. Paracetamol (acetaminophen) for prevention or treatment of pain in newborns. Cochrane Database Syst Rev. 2015;(6):Cd011219.
13.
go back to reference Gibbins S, Stevens BJ, Yamada J, Dionne K, Campbell-Yeo M, Lee G, et al. Validation of the premature infant pain profile-revised (PIPP-R). Early Hum Dev. 2014;90(4):189–93.CrossRefPubMed Gibbins S, Stevens BJ, Yamada J, Dionne K, Campbell-Yeo M, Lee G, et al. Validation of the premature infant pain profile-revised (PIPP-R). Early Hum Dev. 2014;90(4):189–93.CrossRefPubMed
14.
go back to reference Stevens BJRNP, Gibbins SRNP, Yamada JRNP, Dionne KRNMN, Lee GRNM, Johnston CRNDF, et al. The premature infant pain profile-revised (PIPP-R): initial validation and feasibility. Clin J Pain. 2014;30(3):238–43.CrossRefPubMed Stevens BJRNP, Gibbins SRNP, Yamada JRNP, Dionne KRNMN, Lee GRNM, Johnston CRNDF, et al. The premature infant pain profile-revised (PIPP-R): initial validation and feasibility. Clin J Pain. 2014;30(3):238–43.CrossRefPubMed
15.
go back to reference Lee GY, Stevens BJ. Neonatal and infant pain assessment. In: McGrath PJ, Stevens BJ, Walker SM, Zempsky WT, editors. Oxford textbook of paediatric pain. 1st ed. Oxford: Oxford University Press; 2014. p. 353–69. Lee GY, Stevens BJ. Neonatal and infant pain assessment. In: McGrath PJ, Stevens BJ, Walker SM, Zempsky WT, editors. Oxford textbook of paediatric pain. 1st ed. Oxford: Oxford University Press; 2014. p. 353–69.
16.
go back to reference Campbell-Yeo ML, Johnston CC, Joseph KS, Feeley N, Chambers CT, Barrington KJ. Cobedding and recovery time after heel lance in preterm twins: results of a randomized trial. Pediatrics. 2012;130(3):500–6.CrossRefPubMed Campbell-Yeo ML, Johnston CC, Joseph KS, Feeley N, Chambers CT, Barrington KJ. Cobedding and recovery time after heel lance in preterm twins: results of a randomized trial. Pediatrics. 2012;130(3):500–6.CrossRefPubMed
17.
go back to reference Harsha SS, Archana BR. SNAPPE-II (score for neonatal acute physiology with Perinatal extension-II) in predicting mortality and morbidity in NICU. J Clin Diagn Res. 2015;9(10):Sc10–2.PubMedPubMedCentral Harsha SS, Archana BR. SNAPPE-II (score for neonatal acute physiology with Perinatal extension-II) in predicting mortality and morbidity in NICU. J Clin Diagn Res. 2015;9(10):Sc10–2.PubMedPubMedCentral
18.
go back to reference Richardson DK, Corcoran JD, Escobar GJ, Lee SK. SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores. J Pediat. 2001;138(1):92–100.CrossRefPubMed Richardson DK, Corcoran JD, Escobar GJ, Lee SK. SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores. J Pediat. 2001;138(1):92–100.CrossRefPubMed
20.
go back to reference Estabrooks CA, Squires JE, Hutchinson AM, Scott S, Cummings GG, Kang SH, et al. Assessment of variation in the Alberta context tool: the contribution of unit level contextual factors and specialty in Canadian pediatric acute care settings. BMC Health Ser Res. 2011;11(1):1.CrossRef Estabrooks CA, Squires JE, Hutchinson AM, Scott S, Cummings GG, Kang SH, et al. Assessment of variation in the Alberta context tool: the contribution of unit level contextual factors and specialty in Canadian pediatric acute care settings. BMC Health Ser Res. 2011;11(1):1.CrossRef
21.
go back to reference Johnston CC, Fillion F, Campbell-Yeo M, Goulet C, Bell L, McNaughton K, Byron J, Aita M, Finley GA, Walker CD. Kangaroo mothercare diminishes pain from heel lance in very preterm neonates: a crossover trial. BMC Pediatr. 2008;8(1):13.CrossRefPubMedPubMedCentral Johnston CC, Fillion F, Campbell-Yeo M, Goulet C, Bell L, McNaughton K, Byron J, Aita M, Finley GA, Walker CD. Kangaroo mothercare diminishes pain from heel lance in very preterm neonates: a crossover trial. BMC Pediatr. 2008;8(1):13.CrossRefPubMedPubMedCentral
22.
go back to reference Anseloni VC, Weng HR, Terayama R, Letizia D, Davis BJ, Ren K, et al. Age-dependency of analgesia elicited by intraoral sucrose in acute and persistent pain models. Pain. 2002;97(1–2):93–103.CrossRefPubMed Anseloni VC, Weng HR, Terayama R, Letizia D, Davis BJ, Ren K, et al. Age-dependency of analgesia elicited by intraoral sucrose in acute and persistent pain models. Pain. 2002;97(1–2):93–103.CrossRefPubMed
23.
go back to reference Shah PS, Herbozo C, Aliwalas LL, Shah VS. Breastfeeding or breast milk for procedural pain in neonates. Cochrane Database Syst Rev. 2012;12:Cd004950.PubMed Shah PS, Herbozo C, Aliwalas LL, Shah VS. Breastfeeding or breast milk for procedural pain in neonates. Cochrane Database Syst Rev. 2012;12:Cd004950.PubMed
24.
go back to reference Johnston C, Campbell-Yeo M, Fernandes A, Inglis D, Streiner D, Zee R. Skin-to-skin care for procedural pain in neonates. Cochrane Database Syst Rev. 2014;(1):Cd008435. Johnston C, Campbell-Yeo M, Fernandes A, Inglis D, Streiner D, Zee R. Skin-to-skin care for procedural pain in neonates. Cochrane Database Syst Rev. 2014;(1):Cd008435.
25.
go back to reference Cignacco E, Denhaerynck K, Nelle M, Buhrer C, Engberg S. Variability in pain response to a non-pharmacological intervention across repeated routine pain exposure in preterm infants: a feasibility study. Acta Paediatr. 2009;98(5):842–6.CrossRefPubMed Cignacco E, Denhaerynck K, Nelle M, Buhrer C, Engberg S. Variability in pain response to a non-pharmacological intervention across repeated routine pain exposure in preterm infants: a feasibility study. Acta Paediatr. 2009;98(5):842–6.CrossRefPubMed
26.
go back to reference Johnsston CC, Filion F, Snider L, Majnemer A, Limperopoulos C, Walker CD, et al. Routine sucrose analgesia during the first week of life in neonates younger than 31 weeks’ postconceptional age. Pediatrics. 2002;110(3):523-8. Johnsston CC, Filion F, Snider L, Majnemer A, Limperopoulos C, Walker CD, et al. Routine sucrose analgesia during the first week of life in neonates younger than 31 weeks’ postconceptional age. Pediatrics. 2002;110(3):523-8.
27.
go back to reference Stevens B, Yamada J, Beyene J, Gibbins S, Petryshen P, Stinson J, et al. Consistent management of repeated procedural pain with sucrose in preterm neonates: is it effective and safe for repeated use over time? Clin J Pain. 2005;21(6):543–8.CrossRefPubMed Stevens B, Yamada J, Beyene J, Gibbins S, Petryshen P, Stinson J, et al. Consistent management of repeated procedural pain with sucrose in preterm neonates: is it effective and safe for repeated use over time? Clin J Pain. 2005;21(6):543–8.CrossRefPubMed
28.
go back to reference Gaspardo CM, Miyase CI, Chimello JT, Martinez FE, Martins Linhares MB. Is pain relief equally efficacious and free of side effects with repeated doses of oral sucrose in preterm neonates? Pain. 2008;137(1):16–25.CrossRefPubMed Gaspardo CM, Miyase CI, Chimello JT, Martinez FE, Martins Linhares MB. Is pain relief equally efficacious and free of side effects with repeated doses of oral sucrose in preterm neonates? Pain. 2008;137(1):16–25.CrossRefPubMed
29.
go back to reference Taddio A, Shah V, Atenafu E, Katz J. Influence of repeated painful procedures and sucrose analgesia on the development of hyperalgesia in newborn infants. Pain. 2009;144(1–2):43–8.CrossRefPubMed Taddio A, Shah V, Atenafu E, Katz J. Influence of repeated painful procedures and sucrose analgesia on the development of hyperalgesia in newborn infants. Pain. 2009;144(1–2):43–8.CrossRefPubMed
30.
go back to reference Harrison D, Loughnan P, Manias E, Gordon I, Johnston L. Repeated doses of sucrose in infants continue to reduce procedural pain during prolonged hospitalizations. Nurs Res. 2009;58(6):427–34.CrossRefPubMed Harrison D, Loughnan P, Manias E, Gordon I, Johnston L. Repeated doses of sucrose in infants continue to reduce procedural pain during prolonged hospitalizations. Nurs Res. 2009;58(6):427–34.CrossRefPubMed
31.
go back to reference Johnston CC, Filion F, Snider L, Limperopoulos C, Majnemer A, Pelausa E, et al. How much sucrose is too much sucrose? Pediatrics. 2007;119(1):226.CrossRefPubMed Johnston CC, Filion F, Snider L, Limperopoulos C, Majnemer A, Pelausa E, et al. How much sucrose is too much sucrose? Pediatrics. 2007;119(1):226.CrossRefPubMed
32.
go back to reference Banga S, Datta V, Rehan HS, Bhakhri BK. Effect of sucrose analgesia, for repeated painful procedures, on short-term neurobehavioral outcome of preterm neonates: a randomized controlled trial. J Trop Pediat. 2016;62(2):101–6.CrossRef Banga S, Datta V, Rehan HS, Bhakhri BK. Effect of sucrose analgesia, for repeated painful procedures, on short-term neurobehavioral outcome of preterm neonates: a randomized controlled trial. J Trop Pediat. 2016;62(2):101–6.CrossRef
Metadata
Title
The minimally effective dose of sucrose for procedural pain relief in neonates: a randomized controlled trial
Authors
Bonnie Stevens
Janet Yamada
Marsha Campbell-Yeo
Sharyn Gibbins
Denise Harrison
Kimberley Dionne
Anna Taddio
Carol McNair
Andrew Willan
Marilyn Ballantyne
Kimberley Widger
Souraya Sidani
Carole Estabrooks
Anne Synnes
Janet Squires
Charles Victor
Shirine Riahi
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2018
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-018-1026-x

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