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Three Part Question

In [non-ventilated neonates undergoing neonatal procedures] does [oral sucrose] [reduce pain]?

Clinical Scenario

You are a junior doctor working in a neonatal intensive care unit. You are about to take blood from a baby born at 34 weeks gestation who is now 24 hours old and not being ventilated. The neonatal sister suggests you give the baby some oral sucrose before the procedure as analgesia. You have never used sucrose before and are uncertain whether there is any real evidence behind its efficacy.

Search Strategy

Cochrane Database and Medline using the Pubmed interface.
sucrose AND pain AND neonate LIMIT to RCT, 0-23 months age group AND English

Search Outcome

3 systematic reviews, 1 relevant; 23 papers of which 17 were relevant. Of these, 14 were included in the systematic review.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Blass EM and Hoffmeyer LB et al, 1991, USA	54 term babies, 28-54 hours old randomised to 2ml 12% sucrose or 2ml sterile water	RCT (level 1b)	Crying time during procedure and over 3 minutes following procedure	Sucrose with pacifier (compared with sterile water with pacifier) significantly reduced crying time during procedure (expressed as percentage of total procedure time) sucrose 42%, water 80%, p<0.01	Study excluded by Cochrane as the number of neonates in each experimental group not stated
Blass EM et al, 1997, USA	72 neonates, birth weight 2976-3697g, 22- 40 hours old randomised to 2ml of: sucrose, water, similac milk, Ross special formula, dilute fat, concentrated fat, fat/lactose, lactose or protein.	RCT (level 1b)	Crying time during procedure and over 3 minutes following procedure	Sucrose (compared with sterile water) significantly reduced crying time during procedure (expressed as percentage of total procedure time) sucrose 47%, water 92%, p<0.015	As there were 9 experimental groups in this study there were only 8 subjects in each group
Abad F et al, 2001, Spain	51 term babies, <4 days old (55 venepunctures) randomised to 2ml 24% sucrose, 2ml spring water, 1g EMLA or sucrose and EMLA	RCT (level 1b)	Crying time/Heart rate/O2 saturation/Respiratory rate	Sucrose (compared with sterile water as placebo) significantly reduced crying time p=0.001 and heart rate p=0.04. (No absolute figures for crying time or heart rate given)	Study excluded by Cochrane review as 4 babies were included twice as they received 2 venepunctures during study period. The venepunctures were separated by at least 24 hours and the babies were randomized to another arm
Stevens B et al, 2001, Oxford, UK	Systematic review of 17 RCT's comparing sucrose to placebo	Sytematic Review (level 1a)	Behavioural (crying time, quality of suck), physiological (heart rate, respiratory rate, O2 saturation), multidimensional behavioural pain scores	Significant reduction in behavioural and physiological indicators of pain and in multidimensional pain scores e.g.weighted mean difference for pain scores pooled across 3 studies at 30 secs after heel prick -1.64 (95% CI -2.47, -0.81) and at 60 secs -2.05 (95% CI -3.08, -1.02)	Patients studied ranged from 27 weeks to term babies. Doses used in studies were varied, ranging from 0.012 - 0.12g sucrose. Only one study looked at adverse effects. Ten studies were not completely double blinded as they used pacifiers as one of the experimental arms. Frequently studies did not report concealment of randomisation. Overall, however, all included studies were carefully planned and well designed

Comment(s)

All fourteen studies included in the Cochrane Review and the three additional studies quoted above show a significant reduction in indicators of pain when sucrose is used for analgesia in preterm and term neonates undergoing blood sampling. The most consistent effect is the reduction in crying time. Few papers considered adverse effects; those that did suggested that these were minimal including transient desaturation and choking following sucrose administration. Further work is required to elucidate the safety of oral sucrose particularly in very low birth weight babies and others at risk of developing necrotising enterocolitis. Questions have also been raised about early conditioning to sweeteners. No such conditioning has been demonstrated convincingly but there is concern that parents, impressed by the calming effect of sucrose, will continue to use it at home. There is no clear consensus on adequate dose of sucrose. Doses between 0.012g and 1g were shown to be effective in the above studies. In all but three of the studies sucrose was given two minutes prior to the procedure. Sucrose appears to work in a dose-dependent fashion: the higher the dose the greater the reduction in pain.4, 3, 2 Investigators also found that a repeated dose of sucrose is more effective than a single dose.6 There were several other findings in the afore-mentioned studies. Many studies found that sucrose combined with the use of a pacifier has a synergistic effect on pain reduction. One study found that use of a pacifier alone was significantly more analgesic than sucrose used alone. Investigators studying whether sucrose exerts its analgesic effects through a pre- or post-absorptive mechanism found that it is ineffective when administered intragastrically and only reduced pain when given orally. Another trial found that sucrose is more effective than milk and its components in reducing pain. Finally, there is a significant synergistic effect when sucrose is combined with holding the baby throughout the procedure suggesting that a 'caregiving' context is beneficial to pain reduction in neonates.8

Clinical Bottom Line

Sucrose is effective at reducing pain in neonatal procedures and should be used for venepuncture and heelstick sampling. 2 mls of 12% – 50% sucrose should be given 2 minutes before procedure.

Level of Evidence

Level 1 - Recent well-done systematic review was considered or a study of high quality is available.

References

1. Blass EM, Hoffmeyer LB. Sucrose as an analgesic for newborn infants. Pediatrics 1991;87(2):215-8.
2. Haouari N, Wood C, Griffiths G, et al. The analgesic effect of sucrose in full term infants: a randomised controlled trial. BMJ 1995;310(6993):1498-500.
3. Ramenghi LA, Wood CM, Griffith GC, et al. Reduction of pain response in premature infants using intraoral sucrose. Arch Dis Child Fetal Neonatal Ed 1996;74(2):F126-8.
4. Abad F, Diaz NM, Domenech E, et al. Oral sweet solution reduces pain-related behaviour in preterm infants. Acta Paediatr 1996;85(7):854-8.
5. Blass EM. Milk-induced hypoalgesia in human newborns. Pediatrics 1997;99(6):825-9.
6. Johnston CC, Stremler R, Horton L, et al. Effect of repeated doses of sucrose during heel stick procedure in preterm neonates. Biol Neonate 1999 Mar;75(3):160-6.
7. Abad F, Diaz-Gomez NM, Domenech E, et al. Oral sucrose compares favourably with lidocaine-prilocaine cream for pain relief during venepuncture in neonates. Acta Paediatr 2001;90(2):160-5.
8. Stevens B, Yamada J, Ohlsson A. Sucrose analgesia in newborn infants undergoing painful procedures. (Cochrane Review). In The Cochrane Library Issue 3 2001. Oxford. Update Software.