British Journal of Anaesthesia, 2003, Vol. 90, No. 5 642-652
© 2003 The Board of Management and Trustees of the British Journal of Anaesthesia
Clinical Investigations |
Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants
1 Department of Anaesthesiology, 2 Paediatric Surgery and 3 Paediatrics, Erasmus MC/Sophia, Dr Molewaterplein 60, NL-3015 GJ Rotterdam, the Netherlands. 4 Division of Paediatric Clinical Pharmacology, Children’s National Medical Center, Washington, DC, USA. 5 Departments of Paediatrics and Pharmacology, George Washington University Medical Center, Washington, DC, USA. 6 Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, the Netherlands. 7 Department of Paediatrics, Critical Care Medicine Section, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Corresponding author. E-mail: j.bouwmeester.1@erasmusmc.nl
Background. To investigate clinical variables such as gestational age, sex, weight, the therapeutic regimens used and mechanical ventilation that might affect morphine requirements and plasma concentrations of morphine and its metabolites.
Methods. In a double-blind study, neonates and infants stratified for age [group I 0–4 weeks (neonates), group II 
4–26 weeks, group III 26–52 weeks, group IV 1–3 yr] admitted to the paediatric intensive care unit after abdominal or thoracic surgery received morphine 100 µg kg–1 after surgery, and were randomly assigned to either continuous morphine 10 µg kg–1 h–1 or intermittent morphine boluses 30 µg kg–1 every 3 h. Pain was measured using the COMFORT behavioural scale and a visual analogue scale. Additional morphine was administered on guidance of the pain scores. Morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) plasma concentrations were measured before, directly after, and at 6, 12 and 24 h after surgery.
Results. Multiple regression analysis of different variables revealed that age was the most important factor affecting morphine requirements and plasma morphine concentrations. Significantly fewer neonates required additional morphine doses compared with all other age groups (P<0.001). Method of morphine administration (intermittent vs continuous) had no significant influence on morphine requirements. Neonates had significantly higher plasma concentrations of morphine, M3G and M6G (all P<0.001), and significantly lower M6G/morphine ratio (P<0.03) than the older children. The M6G/M3G ratio was similar in all age groups.
Conclusions. Neonates have a narrower therapeutic window for postoperative morphine analgesia than older age groups, with no difference in the safety or effectiveness of intermittent doses compared with continuous infusions in any of these age groups. In infants >1 month of age, analgesia is achieved after morphine infusions ranging from 10.9 to 12.3 µg kg–1 h–1 at plasma concentrations of <15 ng ml–1.
Br J Anaesth 2003; 90: 642–52
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