- Email: [email protected]
Oral sucrose for procedural pain in infants
Correspondence
conclusion, “sucrose should not be used routinely for procedural pain in infants without further investigation”1 unjustified. The selected indices did not recognise pain as engaging widely distributed, serial and parallel, dynamic activation in multiple areas of the brain.3,4 EEG activity was reported for only one of 32 recording electrodes, and thus did not address multiple brain regions that might have been activated.5 The suggestion of dissociation between brain activity and the experience and expression of pain is reminiscent of Descartes’ dualism. The intervention clearly affected behaviour, with the neural measures not identifying the biological substrate. Other methodological issues could account for differences between the neural and behavioural measures. The single control procedure was not randomly ordered. Only 44 of 59 infants were included in the analysis of EEG and premature infant pain profile (34 of 59 in the EMG analysis). These 25% and 42% attrition rates, respectively, might have eliminated infants with vigorous facial displays contributing to dissociation between measures. Although infant pain assessment is imperfect and imprecise, caution should prevail concerning conclusions on well supported pain-relieving strategies. Because one selected measure of neural activity was not responsive to sucrose does not preclude other measures from being responsive. Researchers and clinicians have an ethical responsibility to consider oral sucrose for painful procedures, while doing further effectiveness research using validated cognitive and behavioural assessment measures. We declare that we have no conflicts of interest.
*Bonnie Stevens, Kenneth Craig, Celeste Johnston, Denise Harrison, Arne Ohlsson [email protected] Centre for Nursing, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada (BS); University of British Columbia, Vancouver, BC, Canada (KC);
26
McGill University, Montreal, QC, Canada (CJ); Royal Children’s Hospital, Melbourne, VIC, Australia (DH); and University of Toronto, Toronto, ON, Canada (BS, AO) 1
2
3
4 5
Slater R, Cornelissen L, Fabrizi L, et al. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Lancet 2010; 376: 1225–32. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev 2010; 1: CD001069. Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science 2000; 288: 1769–72. Tracey I. Imaging pain. Br J Anaesth 2008; 101: 32–39. Hofbauer RK, Rainville P, Duncan GH, Bushnell MC. Cortical representation of the sensory dimension of pain. J Neurophysiol 2001; 86: 402–11.
in the context of conclusions were premature infant pain profile and facial expressions, both of which were affected by sucrose, as shown in many earlier studies.5 Development of objective physiological tools for assessment of neonatal pain is a major endeavour, which calls for careful and solid reasoning. Advanced-looking tools might bring a high-impact audience to old discoveries. However, use of unfounded tools will readily bring unsound conclusions, which might sooner or later become counterproductive to the field itself. I declare that I have no conflicts of interest.
Rebeccah Slater and colleagues1 studied the effect of sucrose in treating neonatal pain, and they conclude 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 neurophysiological data considered by Slater and colleagues as the primary outcome measure do not really provide a physiologically sensible bridge to their conclusions. Slater and colleagues call their electroencephalography (EEG) response a “specific nociceptive brain activity”, because they earlier showed it to come after heel lance but not after a tactile touch. It is obvious that a heel lance also results in arousal,2 causing a comparable scalp response, which can even be seen after an auditory stimulus.3 Hence, the EEG response seen by Slater and colleagues is not proven to be specific to the noxiousness of the stimulus. Slater and colleagues also measured spinal reflexes as the other index of pain response. As every neurologist would expect, spinal reflexes to noxa are not affected by sucrose, which naturally works at supraspinal level. The immaturity of descending inhibition4 makes this approach particularily poor in neonates, and useless with respect to Slater and colleagues’ conclusions. The sound measures
Sampsa Vanhatalo sampsa.vanhatalo@helsinki.fi Department of Children’s Clinical Neurophysiology, PO Box 280 (Lastenlinnantie 2), 00029 Helsinki, Finland 1
2
3
4 5
Slater R, Cornelissen L, Fabrizi L, et al. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Lancet 2010; 376: 1225–32. Norman E, Rosén I, Vanhatalo S, et al. Electroencephalographic response to procedural pain in healthy term newborn infants. Pediatr Res 2008; 64: 429–34. Hrbek A, Hrbkova M, Lenard H-G. Somato-sensory, auditory and visual evoked responses in newborn infants during sleep and wakefulness. Electroencephalogr Clin Neurophysiol 1969; 26: 597–603. Fitzgerald M. The development of nociceptive circuits. Nat Rev Neurosci 2005; 6: 507–20. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev 2010; 1: CD001069.
Rebeccah Slater and colleagues1 conclude 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”. In the Summary, they state that “59 newborn infants…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.” In two previous systematic reviews about sucrose,2,3 the single dose commonly used was 2 mL in full-term and preterm infants and 0·5 mL per kg for www.thelancet.com Vol 377 January 1, 2011
conclusion, “sucrose should not be used routinely for procedural pain in infants without further investigation”1 unjustified. The selected indices did not recognise pain as engaging widely distributed, serial and parallel, dynamic activation in multiple areas of the brain.3,4 EEG activity was reported for only one of 32 recording electrodes, and thus did not address multiple brain regions that might have been activated.5 The suggestion of dissociation between brain activity and the experience and expression of pain is reminiscent of Descartes’ dualism. The intervention clearly affected behaviour, with the neural measures not identifying the biological substrate. Other methodological issues could account for differences between the neural and behavioural measures. The single control procedure was not randomly ordered. Only 44 of 59 infants were included in the analysis of EEG and premature infant pain profile (34 of 59 in the EMG analysis). These 25% and 42% attrition rates, respectively, might have eliminated infants with vigorous facial displays contributing to dissociation between measures. Although infant pain assessment is imperfect and imprecise, caution should prevail concerning conclusions on well supported pain-relieving strategies. Because one selected measure of neural activity was not responsive to sucrose does not preclude other measures from being responsive. Researchers and clinicians have an ethical responsibility to consider oral sucrose for painful procedures, while doing further effectiveness research using validated cognitive and behavioural assessment measures. We declare that we have no conflicts of interest.
*Bonnie Stevens, Kenneth Craig, Celeste Johnston, Denise Harrison, Arne Ohlsson [email protected] Centre for Nursing, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada (BS); University of British Columbia, Vancouver, BC, Canada (KC);
26
McGill University, Montreal, QC, Canada (CJ); Royal Children’s Hospital, Melbourne, VIC, Australia (DH); and University of Toronto, Toronto, ON, Canada (BS, AO) 1
2
3
4 5
Slater R, Cornelissen L, Fabrizi L, et al. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Lancet 2010; 376: 1225–32. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev 2010; 1: CD001069. Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science 2000; 288: 1769–72. Tracey I. Imaging pain. Br J Anaesth 2008; 101: 32–39. Hofbauer RK, Rainville P, Duncan GH, Bushnell MC. Cortical representation of the sensory dimension of pain. J Neurophysiol 2001; 86: 402–11.
in the context of conclusions were premature infant pain profile and facial expressions, both of which were affected by sucrose, as shown in many earlier studies.5 Development of objective physiological tools for assessment of neonatal pain is a major endeavour, which calls for careful and solid reasoning. Advanced-looking tools might bring a high-impact audience to old discoveries. However, use of unfounded tools will readily bring unsound conclusions, which might sooner or later become counterproductive to the field itself. I declare that I have no conflicts of interest.
Rebeccah Slater and colleagues1 studied the effect of sucrose in treating neonatal pain, and they conclude 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 neurophysiological data considered by Slater and colleagues as the primary outcome measure do not really provide a physiologically sensible bridge to their conclusions. Slater and colleagues call their electroencephalography (EEG) response a “specific nociceptive brain activity”, because they earlier showed it to come after heel lance but not after a tactile touch. It is obvious that a heel lance also results in arousal,2 causing a comparable scalp response, which can even be seen after an auditory stimulus.3 Hence, the EEG response seen by Slater and colleagues is not proven to be specific to the noxiousness of the stimulus. Slater and colleagues also measured spinal reflexes as the other index of pain response. As every neurologist would expect, spinal reflexes to noxa are not affected by sucrose, which naturally works at supraspinal level. The immaturity of descending inhibition4 makes this approach particularily poor in neonates, and useless with respect to Slater and colleagues’ conclusions. The sound measures
Sampsa Vanhatalo sampsa.vanhatalo@helsinki.fi Department of Children’s Clinical Neurophysiology, PO Box 280 (Lastenlinnantie 2), 00029 Helsinki, Finland 1
2
3
4 5
Slater R, Cornelissen L, Fabrizi L, et al. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Lancet 2010; 376: 1225–32. Norman E, Rosén I, Vanhatalo S, et al. Electroencephalographic response to procedural pain in healthy term newborn infants. Pediatr Res 2008; 64: 429–34. Hrbek A, Hrbkova M, Lenard H-G. Somato-sensory, auditory and visual evoked responses in newborn infants during sleep and wakefulness. Electroencephalogr Clin Neurophysiol 1969; 26: 597–603. Fitzgerald M. The development of nociceptive circuits. Nat Rev Neurosci 2005; 6: 507–20. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev 2010; 1: CD001069.
Rebeccah Slater and colleagues1 conclude 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”. In the Summary, they state that “59 newborn infants…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.” In two previous systematic reviews about sucrose,2,3 the single dose commonly used was 2 mL in full-term and preterm infants and 0·5 mL per kg for www.thelancet.com Vol 377 January 1, 2011