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

BACKGROUND: Many 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. METHODS: In 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. FINDINGS: 29 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). INTERPRETATION: Our 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. FUNDING: Medical Research Council.

Latency to facial expression change following noxious stimulation in infants is dependent on postmenstrual age.

Change in facial expression over a fixed time after a noxious stimulus is the key measure used to calculate pain scores in preterm and newborn infants. We hypothesised that the latency of facial motor responses would be longer in the youngest premature infants and that behavioural scoring methods of pain may need to take this into account. One hundred and seventy-two clinically required heel lances were performed in 95 infants from 25 to 44 weeks postmenstrual age (PMA). Sixty-four percentage of the heel lances evoked a change in facial expression. Change in facial expression was observed in infants across the whole age range from 25 weeks PMA and the latency to the facial expression response ranged from 1 to 17s. Latency to facial expression change was dependent on the infants' PMA at the time of the heel lance. Infants below 32 weeks PMA had a significantly longer latency to change in facial expression than older infants (54% increase in infants below 32 weeks; p < 0.001). Sleep state and presence of brain damage (IVH grades 1-4) did not significantly increase the latency (p > 0.05 for each variable). Intravenous morphine at the time of the heel lance significantly increased the latency to facial expression response (p < 0.001) but the analysis shows that latency is highly dependent on PMA independent of morphine administration. These findings highlight developmental changes underlying infant behaviour that are critically important if pain scores are to be correctly interpreted.