Postoperative pain in the neonate: age-related differences in morphine requirements and metabolism

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 continuous morphine (10 mug/kg per hour) or intermittent morphine (30 mug/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 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 mug/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.