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. 2015 Dec;49(12):1291-7.
doi: 10.1177/1060028015606732. Epub 2015 Sep 14.

Brain Injury and Development in Preterm Infants Exposed to Fentanyl

Christopher McPherson  1 , Matthew Haslam  2 , Roberta Pineda  2 , Cynthia Rogers  2 , Jeffrey J Neil  3 , Terrie E Inder  4
Affiliations

Brain Injury and Development in Preterm Infants Exposed to Fentanyl

Christopher McPherson et al. Ann Pharmacother. 2015 Dec.

Abstract

Background: Fentanyl is commonly used in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl.

Objective: To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants.

Methods: Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤30 weeks gestational age (mean gestational age 26.9 ± 1.8 weeks) who underwent magnetic resonance imaging at term equivalent age. Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age.

Results: Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 µg/kg, interquartile range 1-441 µg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (odds ratio 2.1, 95% confidence interval 1.1-4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates, including the presence of cerebellar hemorrhage (r = 0.461, P = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age.

Conclusions: Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly used analgesic agents in preterm infants.

Keywords: analgesics; magnetic resonance imaging; neonatal intensive care; opioid analgesics; premature infant.

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Conflict of interest statement

Declaration of conflicting interests: The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Log of Fentanyl Dose in Relation to Cerebellar Diameter (d-TCD). Center line represents fitted least-squares regression line and outer lines represent 95% confidence interval.
See this image and copyright information in PMC

References

    1. Fitzgerald M. The development of nociceptive circuits. Nat Rev Neurosci. 2005;6:507–20. - PubMed
    1. Grunau RE, Holsti L, Peters JW. Long-term consequences of pain in human neonates. Semin Fetal Neonatal Med. 2006;11:268–75. - PubMed
    1. Durrmeyer X, Vutskits L, Anand KJ, Rimensberger PC. Use of analgesic and sedative drugs in the NICU: integrating clinical trials and laboratory data. Pediatr Res. 2010;67:117–27. - PubMed
    1. Anand KJ, Hall RW, Desai N, et al. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. Lancet. 2004;363:1673–82. - PubMed
    1. Anand KJ, Barton BA, McIntosh N, et al. Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates. Arch Pediatr Adolesc Med. 1999;153:331–8. - PubMed

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