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.


METHODS
Morphine was infused for 2 to 4 days (140 microg/kg over 1 hour followed by 20 microg/kg/h) to 31 ventilator-treated newborn infants (gestational age, 24 to 41 weeks; birth weight, 765 to 4,015 g). Morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations in serum were determined from 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 were 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.
Saarenmaa
E
E
Hospital for Children and Adolescents, the Department of Clinical Pharmacology, University of Helsinki, Finland.
Neuvonen
P J
PJ
Rosenberg
P
P
Fellman
V
V
D001724:Birth Weight; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000097:blood; D009294:Narcotics / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
D009022:Morphine Derivatives; D009294:Narcotics; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide