MedWire News: Study findings suggest that the maturation of morphine metabolism may be delayed in ventilated preterm neonates, a finding that could be related to severity of illness in such infants.
K. Anand (University of Arkansas for Medical Sciences, Little Rock, USA) and colleagues observe that “there are limited reports of either morphine pharmacokinetics or pharmacodynamics in preterm newborns.”
To investigate, the team analyzed data from the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial relating to 875 preterm neonates born between 23 and 32 weeks’ gestation. These data were compared with evidence on morphine pharmacology from a previous study of 184 infants born at term. Predicted values for maturation of morphine clearance were calculated using statistical modeling.
The NEOPAIN infants were randomly assigned to receive placebo or morphine, comprising an initial intravenous dose followed by infusions for up to 14 days. Morphine pharmacokinetic and pharmacodynamic parameters were measured at 20 to 28 hours and at 70 to 76 hours after starting the drug infusion, and again 10 to 14 hours after drug discontinuation. Neonatal response to endotracheal tube (ETT) suctioning was also evaluated.
Anand et al report that in preterm neonates, morphine clearance increased with gestational age. Based on the theory that transition from the intrauterine to the extrauterine environment may accelerate certain metabolic activities, the researchers hypothesized that the maturation of morphine clearance would occur at earlier postmenstrual ages in preterm than term infants.
However, using statistical modeling the opposite relationship was observed, with preterm infants showing a lower predicted level of morphine clearance compared with term infants of the same postmenstrual age.
The volume of distribution was also greater in preterm than term neontates, but morphine did not show any significant impact on the neonatal response to ETT suctioning.
Writing in the British Journal of Anaesthesia, the authors speculate that the unexpected findings regarding morphine clearance may reflect the severity of illness in the preterm neonates, “a supposition supported by data suggesting morphine clearance maturation occurs more quickly in infants undergoing noncardiac surgery than those undergoing cardiac surgery, and also the reduced clearance reported in critically ill neonates.”