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

Abstract

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.

Figure 1

Experimental time line EEG=electroencephalography. EMG=electromyography.

Figure 2

Trial profile EEG=electroencephalography. PIPP=premature infant pain profile. EMG=electromyography.

Figure 3

Characterisation of the nociceptive-specific brain activity (A) and effect of sucrose or sterile water on the nociceptive-specific brain activity (B) (A) Average waveform of the group data after (i) noxious heel lance and (ii) non-noxious control stimulus (alignment window 400–750 ms). (iii) Mean (SE) weight of the second principal component after the noxious heel lance and non-noxious control stimulus (*p=0·006). (B) Average waveform of the group data after the noxious heel lance, separated into two groups: (i) infants administered sucrose and (ii) infants administered sterile water (alignment window 400–750 ms). (iii) Mean (SE) weight of the nociceptive-specific component in the sucrose and sterile water groups (p=0·46).

Figure 4

Characterisation of the spinal nociceptive reflex withdrawal activity (A) and effect of sucrose or sterile water on spinal nociceptive reflex withdrawal activity (B) (A) Example spinal reflex withdrawal activity in one infant after: (i) noxious heel lance and (ii) non-noxious control stimulus. (iii) Magnitude (mean [SE]) of the spinal reflex withdrawal activity after noxious heel lance and non-noxious control stimulus represented as the root mean square (RMS) activity in 250 ms time periods in infants. (iv) Mean (SE) spinal reflex withdrawal activity in infants after the noxious heel lance and non-noxious control stimulus (*p<0·0001). (B) Example spinal nociceptive reflex withdrawal activity after a noxious heel lance in two infants who received: (i) sucrose and (ii) sterile water. (iii) Magnitude (mean [SE]) of the spinal nociceptive reflex withdrawal activity after noxious heel lance in infants given sucrose or sterile water represented as the RMS activity in 250 ms time periods. (iv) Mean (SE) spinal nociceptive reflex withdrawal activity in infants given sucrose or sterile water (p=0·49).