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

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, 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

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).

Keywords: Adverse event; Analgesia; Heel lance; NICU; Neonates; PIPP-R; Pain; Preterm infants; Sucrose.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Research Ethics Boards at The Hospital for Sick Children (1000038052), Sunnybrook Health Sciences Centre (354–2013), IWK Health Centre (1013855), The Ottawa Hospital (20130327-01H), and Children’s Hospital of Eastern Ontario (13/12E). Informed written consent was obtained from a parent prior to study enrollment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Consort flow diagram of all neonates in participating NICUs screened for eligibility and randomized to sucrose intervention groups. Reasons for exclusion included not meeting inclusion criteria, refusals to participate, and other reasons [e.g., exclusion criteria, medical refusal (palliative care, social issues, and multiple research studies), isolation precautions, and researcher or parents unavailable for consent discussion]

References

    1. 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):153–161. doi: 10.1155/2013/956549.
    1. 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.
    1. 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):500–515. doi: 10.1542/peds.2013-2744.
    1. 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):153–155. doi: 10.1097/AJP.0b013e3181847a09.
    1. 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):129–136. doi: 10.1111/apa.13210.
    1. 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):119–120. doi: 10.1111/apa.13255.
    1. 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. doi: 10.1542/peds.2010-1593.
    1. . A comprehensive internet-based randomization service for clinical trials. (2015). Accessed 11 Apr 2017.
    1. 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. doi: 10.1097/00006199-199901000-00006.
    1. 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):239–249. doi: 10.1093/chemse/19.3.239.
    1. 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.
    1. Ohlsson A, Shah PS. Paracetamol (acetaminophen) for prevention or treatment of pain in newborns. Cochrane Database Syst Rev. 2015;(6):Cd011219.
    1. 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):189–193. doi: 10.1016/j.earlhumdev.2014.01.005.
    1. 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):238–243. doi: 10.1097/AJP.0b013e3182906aed.
    1. Lee GY, Stevens BJ. Neonatal and infant pain assessment. In: McGrath PJ, Stevens BJ, Walker SM, Zempsky WT, editors. Oxford textbook of paediatric pain. 1. Oxford: Oxford University Press; 2014. pp. 353–369.
    1. 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):500–506. doi: 10.1542/peds.2012-0010.
    1. 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–Sc12.
    1. 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. doi: 10.1067/mpd.2001.109608.
    1. Patsopoulos NA. A pragmatic view on pragmatic trials. Dialogues Clin Neurosci. 2011;13(2):217–224.
    1. 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. doi: 10.1186/1472-6963-11-1.
    1. 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. doi: 10.1186/1471-2431-8-13.
    1. 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. doi: 10.1016/S0304-3959(02)00010-6.
    1. Shah PS, Herbozo C, Aliwalas LL, Shah VS. Breastfeeding or breast milk for procedural pain in neonates. Cochrane Database Syst Rev. 2012;12:Cd004950.
    1. 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.
    1. 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):842–846. doi: 10.1111/j.1651-2227.2008.01203.x.
    1. 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.
    1. 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):543–548. doi: 10.1097/01.ajp.0000149802.46864.e2.
    1. 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. doi: 10.1016/j.pain.2007.07.032.
    1. 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):43–48. doi: 10.1016/j.pain.2009.02.012.
    1. 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):427–434. doi: 10.1097/NNR.0b013e3181b4b5e4.
    1. 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. doi: 10.1542/peds.2006-3001.
    1. 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):101–106. doi: 10.1093/tropej/fmv079.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi