Relationship Between Opioid Therapy, Tissue-Damaging Procedures, and Brain Metabolites as Measured by Proton MRS in Asphyxiated Term Neonates

To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 nonopioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), andN-acetylaspartate (NAA)/choline (Cho) (p 0.03) and higher Cho/Cr and glutamate/glutamine (Glx) Cr (p 0.02) correlated with increased TDP incidence in the first 2 d of life (DOL). We also found that occipital gray matter (OGM) NAA/Cr was decreased (p= 0.03) and lactate (Lac) was present in a significantly higher amount (40%;p= 0.03) in nonopioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 24 DOL and may provide a degree of neuroprotection. Abbreviations: BGbasal ganglia; Chocholine; Crtotal creatine; Glxglutamate/glutamine; Insmyoinositol; MRSImagnetic resonance spectroscopic imaging; NAAN-acetylaspartate; OGMoccipital gray matter; PCPCSPediatric Cerebral Performance Category Scale; PCrphosphocreatine; SVSsingle-voxel spectroscopy; TEecho delay time; THthalami; TRrepetition time.