title: Neuroimaging, Pain Sensitivity, and Neuropsychological Functioning in School-Age Neonatal Extracorporeal Membrane Oxygenation Survivors Exposed to Opioids and Sedatives.
abstract: OBJECTIVE
  Animal studies found negative long-term effects of exposure to sedatives and opioids in early life, especially when administered in the absence of pain. Around the world, children who require extracorporeal membrane oxygenation receive opioids and sedatives for extended periods, generally in the absence of major pain as extracorporeal membrane oxygenation cannulation is considered minor surgery. Therefore, our objective was to determine the long-term effects of extracorporeal membrane oxygenation treatment with respect to pain sensitivity, brain functioning during pain, brain morphology, and neuropsychological functioning in humans.
  
  
  METHODS
  Prospective follow-up study.
  
  
  METHODS
  Level III university hospital.
  
  
  METHODS
  Thirty-six extracorporeal membrane oxygenation survivors (8.1-15.5 yr) and 64 healthy controls (8.2-15.3 yr).
  
  
  RESULTS
  We measured detection and pain thresholds, brain activity during pain (functional MRI), brain morphology (high-resolution structural MRI), and neuropsychological functioning and collected information regarding the subject's experience of chronic pain. We found a significant difference in the detection threshold for cold measured in a reaction time-dependent fashion (extracorporeal membrane oxygenation group, 29.9°C [SD, 1.4]; control group, 30.6°C [SD, 0.8]; p < 0.01), but no differences in other modalities or in pain sensitivity between groups. Furthermore, no differences in brain activation during pain, brain morphology, or in the occurrence of chronic pain were observed. However, extracorporeal membrane oxygenation survivors performed significantly worse on a verbal memory test compared with controls (p = 0.001).
  
  
  CONCLUSIONS
  While the most critically ill newborns receive extracorporeal membrane oxygenation and, relatedly, large doses of opioids and sedatives for extended periods, global measures of pain sensitivity and neurobiological and neuropsychological development appear to have minor long-term consequences. Possible memory deficits in extracorporeal membrane oxygenation survivors require additional study, but neonatal extracorporeal membrane oxygenation treatment and associated exposure to opioids and sedatives seem less harmful to humans than expected from animal studies.
authors.affiliation: 1Intensive Care Unit and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 2Department of Radiology, Erasmus MC, Rotterdam, The Netherlands. 3Division of Neonatology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 4Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Gerbrich E
authors.initials: GE
authors.lastname: van den Bosch
authors.forename: Hanneke
authors.initials: H
authors.lastname: IJsselstijn
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Monique
authors.initials: M
authors.lastname: van Dijk
authors.forename: Tonya
authors.initials: T
authors.lastname: White
mesh_terms: D000293:Adolescent; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D001921:Brain / Q000502:physiology*; D002648:Child; D016638:Critical Illness / Q000628:therapy*; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D005500:Follow-Up Studies; D006785:Hospitals, University; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009482:Neurophysiology; D009483:Neuropsychological Tests; D017288:Pain Threshold / Q000502:physiology*; D011446:Prospective Studies; D017741:Survivors
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives