Highlights
- •Opioids are commonly used in the NICU and have both beneficial and adverse short-term effects.
- •Long-term follow-up studies on neonatal morphine administration in humans are scarce.
- •Neonatal morphine infusion has no long-term adverse effects on thermal pain thresholds.
- •No effects on neurological functioning or incidence of chronic pain have been observed.
Abstract
Short-term and long-term effects of neonatal pain and its analgesic treatment have
been topics of translational research over the years. This study aimed to identify
the long-term effects of continuous morphine infusion in the neonatal period on thermal
pain sensitivity, the incidence of chronic pain, and neurological functioning. Eighty-nine
of the 150 participants of a neonatal randomized controlled trial on continuous morphine
infusion versus placebo during mechanical ventilation underwent quantitative sensory
testing and neurological examination at the age of 8 or 9 years. Forty-three children
from the morphine group and 46 children from the placebo group participated in this
follow-up study. Thermal detection and pain thresholds were compared with data from
28 healthy controls. Multivariate analyses revealed no statistically significant differences
in thermal detection thresholds and pain thresholds between the morphine and placebo
groups. The incidence of chronic pain was comparable between both groups. The neurological
examination was normal in 29 (76%) of the children in the morphine group and 25 (61%)
of the children in the control group (P = .14). We found that neonatal continuous morphine infusion (10 μg/kg/h) has no adverse
effects on thermal detection and pain thresholds, the incidence of chronic pain, or
overall neurological functioning 8 to 9 years later.
Perspective
This unique long-term follow-up study shows that neonatal continuous morphine infusion
(10 μg/kg/h) has no long-term adverse effects on thermal detection and pain thresholds
or overall neurological functioning. These findings will help clinicians to find the
most adequate and safe analgesic dosing regimens for neonates and infants.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial.Lancet. 2004; 363: 1673-1682
- Opioid neurotoxicity: comparison of morphine and tramadol in an experimental rat model.Int J Neurosci. 2004; 114: 1001-1011
- Projections from the rat cuneiform nucleus to the A7, A6 (locus coeruleus), and A5 pontine noradrenergic cell groups.J Chem Neuroanat. 2013; 50-51: 11-20
- Opioids for neonates receiving mechanical ventilation. a systematic review and meta-analysis.Arch Dis Child-Fetal. 2009; 95: 241-251
- Morphine does not provide adequate analgesia for acute procedural pain among preterm neonates.Pediatrics. 2005; 115: 1494-1500
- Thermal detection thresholds in 5-year-old preterm born children.Early Hum Dev. 2012; 88: 487-491
- Long-term effects of routine morphine infusion in mechanically ventilated neonates on children's functioning: five-year follow-up of a randomized controlled trial.Pain. 2011; 152: 1391-1397
- Does neonatal morphine use affect neuropsychological outcomes at 8 to 9 years of age?.Pain. 2013; 154: 449-458
- A pilot study of preemptive morphine analgesia in preterm neonates: effects on head circumference, social behavior, and response latencies in early childhood.Neurotoxicol Teratol. 2012; 34: 47-55
- Body index measurements in 1996-7 compared with 1980.Arch Dis Child. 2000; 82: 107-112
- Morphine inhibits Purkinje cell survival and dendritic differentiation in organotypic cultures of the mouse cerebellum.Exp Neurol. 1994; 130: 95-105
- Long-term alteration of pain sensitivity in school-aged children with early pain experiences.Pain. 2006; 125: 278-285
- Pain in neonates is different.Pain. 2011; 152: S65-S73
- Effects of neonatal stress and morphine on murine hippocampal gene expression.Pediatr Res. 2010; 69: 285-292
- Minor neurological dysfunction and IQ in 9-year-old children born at term.Dev Disabil Res Rev. 2011; 53: e16-25
- WISC-III NL Wechsler Intelligence Scale for Children.in: Derde Editie N.L. Handleiding en Verantwoording. Harcourt Test Publishers/Nederlands Instituut voor Psychologen, Amsterdam2005
- Cerebellum: links between development, developmental disorders and motor learning.Front Neuroanat. 2012; 6: 1-10
- Pain in children and adolescents: a common experience.Pain. 2000; 87: 51-58
- Long-term consequences of early infant injury and trauma upon somatosensory processing.Eur J Pain. 2007; 11: 799-809
- Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial.JAMA. 2003; 290: 2419-2427
- Long-term effects of neonatal surgery on adulthood pain behavior.Pain. 2005; 113: 347-353
- Influence of repeated painful procedures and sucrose analgesia on the development of hyperalgesia in newborn infants.Pain. 2009; 144: 43-48
- The pharmacological treatment of neonatal pain.Semin Fetal Neonat Med. 2005; 10: 195-205
- Functional MRI pain studies in children? Yes, we (s)can!.Pediatr Radiol. 2013; 43: 1235-1236
- Effects of neonatal stress and morphine on kappa opioid receptor signaling.Neonatology. 2009; 96: 235-243
- Long-term impact of neonatal intensive care and surgery on somatosensory perception in children born extremely preterm.Pain. 2009; 141: 79-87
- Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment.JAMA. 2008; 300: 1665-1673
- Optimal locally robust M-estimates of regression.J Stat Plan Inference. 1997; 64: 309-323
Article info
Publication history
Published online: June 25, 2015
Accepted:
June 15,
2015
Received in revised form:
May 29,
2015
Received:
March 25,
2015
Footnotes
No funding sources were provided.
None of the authors report financial relationships that are relevant to this work. None of the authors report a conflict of interest.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
Identification
Copyright
© 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
