title: Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism.
abstract: OBJECTIVE
  To investigate age-related differences in morphine requirements and metabolism in full-term neonates.
  
  
  METHODS
  Randomized double-blind study in the pediatric surgical intensive care unit.
  
  
  METHODS
  Sixty-eight neonates (52 aged under 7 days, 16 aged 7 day or older) following major surgery.
  
  
  METHODS
  After surgery patients were randomly assigned to continuous morphine (10 micro g/kg per hour) or intermittent morphine (30 micro g/kg per 3 hours). Additional morphine was administered on guidance of pain scores.
  
  
  RESULTS
  Pain was measured by the Comfort behavioral scale and visual analogue scale. Morphine and morphine-6-glucuronide (M6G) plasma concentrations were determined before and 0, 6, 12, and 24 h after surgery. The younger neonates differed significantly from the older neonates in morphine requirement (median 10 vs. 10.8 micro g/kg per hour), morphine plasma concentration [23.0 vs. 15.3 ng/ml), and M6G/morphine ratio (0.6 vs. 1.5). Pain scores did not differ between age groups or morphine treatment groups. Neonates who were mechanically ventilated longer than 24 h had significantly higher morphine plasma concentrations than the spontaneously breathing neonates 12 and 24 h after surgery (29.1 vs. 13.1 ng/ml and 26.9 vs. 12.0 ng/ml, respectively). Morphine plasma concentrations were not correlated with analgesia or respiratory depression. Five neonates (intermittent morphine) showed respiratory insufficiency; however, the difference between the groups was not significant.
  
  
  CONCLUSIONS
  Neonates aged 7 days or younger require significantly less morphine postoperatively than older neonates. The two morphine regimens (continuous, intermittent) were equally effective and safe. Mechanical ventilation decreases morphine metabolism and clearance.
authors.affiliation: Department of Anesthesia, Erasmus Medical Center/Sophia Children's Hospital Rotterdam, Dr Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands. j.bouwmeester.1@erasmusmc.nl
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Bouwmeester
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Monique
authors.initials: M
authors.lastname: van Dijk
authors.forename: K J S
authors.initials: KJ
authors.lastname: Anand
authors.forename: John N
authors.initials: JN
authors.lastname: van den Anker
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
mesh_terms: D000367:Age Factors; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001724:Birth Weight; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D009022:Morphine Derivatives / Q000097:blood; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000139:chemically induced; D012449:Safety; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine