PEDIATRIC PHARMACOLOGY AND THERAPEUTICS Postoperative morphine infusion in newborn infants." Assessment of disposition characteristics and safety Twelve newborn infants were given morphine intravenously for postoperative analgesia. They received a continuous infusion of 6.2 to 40 #g/kg/hrfor 9 to 105 hours (mean +_ SEM 59.5 + 10.2 hours); in four the infusion was preceded by a loading dose of .50 to 100 I~g/kg. Morphine plasma concentrations correlated with the rate of infusion, but with large variability. There was a tendency for plasma morphine concentrations to decrease in some patients receiving a constant infusion rate, suggesting improvement in morphine clearance rate. Elimination half-life of morphine (13.9 +_ 6.4 hours) was significantly longer than in older children and adults (about 2 hours). Similarly, morphine concentrations in neonates receiving 20 #g/kg/hr for 24 hours were three times higher (52 + 31 ng/ml) than in older children receiving the same schedule. Two infants who received 32 and40 #g/kg/hr, respectively, developed generalized seizures. Because of the apparently greater sensitivity to morphine and the lower elimination rate in newborn infants, the infused dose should not exceed 15 #g/kg/hr. (J PeotArR 1985;107.'963-967) Gideon Koren, M.D., Warwick Butt, M.D., Herbert Chinyanga, M.D., Steven Soldin, Ph.D., Yok-Kwang Tan, and Karen Pape, M.D. Toronto, Ontario, Canada MORPHINE INFUSION for postoperative analgesia has been described in adults ~and children,2 but information is lacking on the use of morphine in the newborn infant. We report the results of a prospective study that assessed the safety and disposition characteristics of morphine in neo- nates, METHODS Twelve neonates of gestational ages 35 to 41 weeks (mean + SEM 39.2 _+ 0.5 weeks) and birth weights 2.2 to 4.2 kg (mean 3.3 + 0.2 kg) were studied at postnatal age 9.5 + 4.3 days (range 1 to 49 days). These data, the From the Divisions of Clinical Pharmacology and Neonatology, Department of Pediatrics, and the Departments of Anesthesiolo- gy and Biochemistry, The Research Institute, The Hospital for Sick Children, and the Departments of Pediatrics and Pharma- cology, University of Toronto. Dr. Koren is a fellow of the Medical Research Council of Canada. Submitted for publication March 12, 1985; accepted June 5, 1985. Reprint requests: Gideon Koren, M.D., Division of Clinical Pharmacology, The Hospital for Sick Children, 555 University Ave., Toronto, Ont., Canada M5G 1)(8. medical conditions, and morphine schedules are summa- rized in Table I. This study was approved by the hospital Human Experimentation Review Committee, and informed consent was given by the parents. None of the neonates received morphine during surgery; its use was started after the neonates returned from surgery. The first four patients received a morphine loading dose of 50 to 100 #g/kg, followed by infusion of 6.2 to 40 t~g/kg/hr. The loading dose was intended to achieve an effective level, and was derived from a study in infants and small children.3 The infusion rate had been extrapolated from studies in adults, 4 but because of seizures associated with morphine infusion in two of four patients receiving a bolus, the other eight patients received a morphine infusion of 18.2 to 24 /~g/kg/hr without a loading dose. The morphine sulfate was diluted in 50 ml 5% dextrose solution, and was infused at a rate of 1 to 2 ml/hr. This method of delivery was consistent in all cases. The rate of infusion was controlled by infusion pump. In some patients the infusion rate was changed during therapy (Table I). The duration of morphine infusion ranged from 3.5 to 105 hours (mean 59.5 + 10.2 hours). During the first day after surgery, two patients received TheJournalofPEDIATRICS 963