Received: 23 July 2002 Accepted: 4 June 2003 Published online: 25 July 2003 © Springer-Verlag 2003 The study was supported by The Nether- lands Research Council (NWO, The Hague) and the Sophia Foundation for Medical Research. J. N. van den Anker Departments of Pediatrics and Pharmacology, George Washington University Medical Center, Washington, D.C., USA who were mechanically ventilated longer than 24 h had significantly higher morphine plasma concentra- tions than the spontaneously breath- ing neonates 12 and 24 h after sur- gery (29.1 vs. 13.1 ng/ml and 26.9 vs. 12.0 ng/ml, respectively). Mor- phine plasma concentrations were not correlated with analgesia or res- piratory depression. Five neonates (intermittent morphine) showed res- piratory insufficiency; however, the difference between the groups was not significant. Conclusions: Neo- nates aged 7 days or younger require significantly less morphine postoper- atively than older neonates. The two morphine regimens (continuous, in- termittent) were equally effective and safe. Mechanical ventilation de- creases morphine metabolism and clearance. Keywords Pediatric surgery · Postoperative pain management · Morphine · Morphine-6-glucuronide · Full-term neonates · Mechanical ventilation Intensive Care Med (2003) 29:2009–2015 DOI 10.1007/s00134-003-1899-4 NEONATAL AND PEDIATRIC INTENSIVE CARE Nancy J. Bouwmeester Wim C. J. Hop Monique van Dijk K. J. S. Anand John N. van den Anker Dick Tibboel Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism N. J. Bouwmeester ( ✉ ) Department of Anesthesia, Erasmus Medical Center/ Sophia Children’s Hospital Rotterdam, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands e-mail: j.bouwmeester.1@erasmusmc.nl Tel.: +31-10-4636020 Fax: +31-10-4636804 N. J. Bouwmeester · M. van Dijk D. Tibboel Department of Pediatric Surgery, Erasmus Medical Center/ Sophia Children’s Hospital, Rotterdam, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands W. C. J. Hop Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands K. J. S. Anand Department of Pediatrics, Critical Care Medicine Section, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Ark., USA J. N. van den Anker Division of Pediatric Clinical Pharmacology, Children’s National Medical Center, Washington, D.C., USA Abstract Objective: To investigate age-related differences in morphine requirements and metabolism in full- term neonates. Design and setting: Randomized double-blind study in the pediatric surgical intensive care unit. Patients: Sixty-eight neonates (52 aged under 7 days, 16 aged 7 day or older) following major surgery. Interventions: After surgery patients were randomly assigned to continu- ous morphine (10 μg/kg per hour) or intermittent morphine (30 μg/kg per 3 hours). Additional morphine was administered on guidance of pain scores. Measurements and results: Pain was measured by the Comfort behavioral scale and visual analogue scale. Morphine and morphine-6- glucuronide (M6G) plasma concen- trations were determined before and 0, 6, 12, and 24 h after surgery. The younger neonates differed signifi- cantly from the older neonates in morphine requirement (median 10 vs. 10.8 μg/kg per hour), morphine plasma concentration [23.0 vs. 15.3 ng/ml), and M6G/morphine ra- tio (0.6 vs. 1.5). Pain scores did not differ between age groups or mor- phine treatment groups. Neonates