Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants

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Abstract
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 (Pvs continuous) had no significant influence on morphine requirements. Neonates had significantly higher plasma concentrations of morphine, M3G and M6G (all PP1 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 –1. Br J Anaesth 2003; 90: 642–52