Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial

Abstract

SummaryBackgroundMany infants admitted to hospital undergo repeated invasive procedures. Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores. We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants.MethodsIn this double-blind, randomised controlled trial, 59 newborn infants at University College Hospital (London, UK) were randomly assigned to receive 0·5 mL 24% sucrose solution or 0·5 mL sterile water 2 min before undergoing a clinically required heel lance. Randomisation was by a computer-generated randomisation code, and researchers, clinicians, participants, and parents were masked to the identity of the solutions. The primary outcome was pain-specific brain activity evoked by one time-locked heel lance, recorded with electroencephalography and identified by principal component analysis. Secondary measures were baseline behavioural and physiological measures, observational pain scores (PIPP), and spinal nociceptive reflex withdrawal activity. Data were analysed per protocol. This study is registered, number ISRCTN78390996.Findings29 infants were assigned to receive sucrose and 30 to sterilised water; 20 and 24 infants, respectively, were included in the analysis of the primary outcome measure. Nociceptive brain activity after the noxious heel lance did not differ significantly between infants who received sucrose and those who received sterile water (sucrose: mean 0·10, 95% CI 0·04–0·16; sterile water: mean 0·08, 0·04–0·12; p=0·46). No significant difference was recorded between the sucrose and sterile water groups in the magnitude or latency of the spinal nociceptive reflex withdrawal recorded from the biceps femoris of the stimulated leg. The PIPP score was significantly lower in infants given sucrose than in those given sterile water (mean 5·8, 95% CI 3·7–7·8 vs 8·5, 7·3–9·8; p=0·02) and significantly more infants had no change in facial expression after sucrose administration (seven of 20 [35%] vs none of 24; p<0·0001).InterpretationOur data suggest that oral sucrose does not significantly affect activity in neonatal brain or spinal cord nociceptive circuits, and therefore might not be an effective analgesic drug. The ability of sucrose to reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief.FundingMedical Research Council.

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

“…Slater et al 45 found no differences in nociceptive brain activity or in the magnitude or latency of the spinal nociceptive reflexes after the heel stick, between infants who received sucrose and those who received water, although Premature Infant Pain Profile scores and pain-related facial expressions were significantly reduced in the sucrose-treated infants. These findings contradict data from a large body of literature supporting the analgesic efficacy of sucrose or other sweet solutions.…”

“…These findings contradict data from a large body of literature supporting the analgesic efficacy of sucrose or other sweet solutions. Moreover, there are several methodological concerns related to the Slater et al study 45 that make it seem premature to conclude that sucrose is ineffective based only on its findings. 46 Although the differences between the sucrose and combination groups in behavioral and physiologic scores during the recovery phase were statistically significant, the magnitude of these differences is probably not clinically meaningful.…”

Prevention and Management of Procedural Pain in the Neonate: An Update

“…It has been extensively studied for this purpose, yet many gaps in knowledge remain, including appropriate dosing, mechanism of action, soothing versus analgesic effects, and long-term consequences. [71][72][73] A meta-analysis of 57 studies including >4730 infants with gestational ages ranging from 25 to 44 weeks concluded that sucrose is safe and effective for reducing procedural pain from a single event. 74 Maximum reductions in physiologic and behavioral pain indicators have been noted when sucrose was administered ∼2 minutes before a painful stimulus, and the effects lasted ∼4 minutes.…”

“…76 In animal studies, the analgesic effects of sucrose appear to be a sweet-taste-mediated response of opiate, endorphin, and possibly dopamine or acetylcholine pathways; however, the mechanism of action is not well understood in human neonates. 72,[77][78][79][80][81] An additive analgesic effect has been noted when sucrose is used in conjunction with other nonpharmacologic measures, such as nonnutritive sucking and swaddling, especially for procedures such as ophthalmologic examinations and immunizations. 74,78 Although the evidence that oral sucrose alleviates procedurally related pain and stress, as judged by clinical pain scores, appears to be strong, a small RCT found no difference in either nociceptive brain activity on electroencephalography or spinal nociceptive reflex withdrawal on electromyography between sucrose or sterile water administered to term infants before a heel lance.…”

Sucrose and Warmth for Analgesia in Healthy Newborns: An RCT

“…Although using sucrose use is safe, [19][20][21][22][23] it does not prevent later exaggerated pain response, 24,25 and its mechanism of action is not fully understood. 26,27 Finally, the evidence is inconclusive on whether multiple doses of sucrose may alter later development. Preterm infants (,31 weeks' estimated gestational age) who received sucrose for all painful procedures during their first 7 days had lower neurodevelopmental scores at term, 18 particularly if they received .10 doses per day.…”