Morphine clearance and effects in newborn infants in relation to gestational age

Objective: We sought to provide a rational basis for morphine administration in preterm infants in the immediate postnatal period by determining the clearance and evaluating the efficacy and adverse effects of a continuous infusion. Study design: Morphine was infused for 2 to 4 days (140 mu g/kg over 1 hour followed by 20 mu g/kg/h) to 31 ventilator-treated newborn infants (gestational age, 24 to 41 weeks; birth weight, 765 to 4015 g), Morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations in serum were deter mined fi om arterial blood obtained at 2, 12, 24, 48, and 60 hours after the start of morphine infusion at a median postnatal age of 10 hours. Results: The mean +/- SD steady-state morphine concentration, 167 +/- 77 ng/mL, was achieved between 24 and 48 hours of infusion, and morphine-6-glucuronide and morphine-3-glucuronide concentrations did not reach steady state within 60 hours. Morphine clearance (range, 0.8 to 6.5 mL/min/kg) correlated significantly with gestational age (r = 0.60; P <.01) and birth weight (r = 0.55; P <.01). Pain relief did not correlate with the steady-state morphine concentration. However, significantly higher morphine concentrations a ere found in infants with decreased gastrointestinal motility (187 +/- 82 ng/mL) compared with those without (128 +/- 51 ng/mL; P <.05). Conclusions: Morphine should be used with caution in prematurely born infants because of its low clearance, which correlates with gestational age.